The interns are cramming for their boards and everyone wishes they could get their hands on Callie's notes because she was ranked first in her year. Meanwhile, Burke is trying to get Cristina to sample cakes for the wedding, even though she doesn't care.
Meredith feels bad for telling Derek he was "hovering" so she says she's going to communicate more, but she can't see that he's the one who's being withdrawn and distant now.
George and Izzie congratulate themselves on how they've put their mistake behind them and have gone back to just being friends.
The chairman of the hospital board, Larry Jenning, is admitted with a delicate situation: His testicles are horribly swollen after his trip to the Amazon. Accompanying him is assistant, Celeste, who tells them she'll need to be tested too since she's having an affair with Larry. Addison and George examine her and she thinks they must be judging her for sleeping with a married man and they are quick to reassure her that's not the case.
Jenning wants Richard himself to work on him, not to delegate the job. He accuses Richard of losing his edge as a surgeon and becoming just a politician. And that maybe he was wrong to name Richard as Chief of Surgery in the first place and it might be best if he is stepping down after all.
Jenning's X ray reveals a rare fish that swam up his penis when he urinated in the Amazon river! It's now lodged in his bladder and could lead to sepsis unless they operate immediately. George tells Celeste that she's not in danger but that Larry has gone into surgery. She admits that she's thinking of leaving Larry, just as his wife shows up.
A man who's had a runny nose for weeks comes into the clinic for the fourth time and Izzie tells him it's just a cold. Sydney, who's running the clinic for the day, says that might have been fine with Miranda, but she's going to make sure the patient gets full care under her watch. She orders Izzie to do a nasal lavage. Miranda stops in and wants to send the man home, but when she sees blood on the pillow, she orders a CT scan instead. It turns out he was leaking spinal fluid through his nose because of a brain herniation. Miranda feels terrible about having sent him home three times before and insists on scrubbing in.
Mark reminds Addison of their "no sex with anyone else" bet and that there's only 28 days left to go. She's less than enthusiastic. Since Ava is on bedrest near the nurse's station, she's heard all the hospital gossip, including about their bet. She tells Alex, after she apologizes for yelling at him. Addison notes how attentive Alex is being to Ava and wishes someone were as concerned about her blood pressure. Alex says he's pretty sure in 28 days, Mark will be.
Addison confides in Callie that she wants someone who will barbecue and teach kids to play ball and she doesn't think either Mark or Alex are that guy, even if she can't stop thinking about Alex. Callie thinks Alex could be and that his bad boy days are behind him. She reveals that she knows George was with Izzie when he said he wasn't. She's sure it's nothing but Addison tells her that her instincts are probably right.
Ava overhears their conversation and urges Alex to go after Addison, since she wants him and not Mark. Just then, she starts seizing. The baby is in distress, so they need to do an emergency C section. Ava panics but Alex assures her she's ready and she's not alone. After the delivery, they take the baby away and she starts to freak out. Alex goes to comfort her and her blood pressure returns to normal.
Addison angrily confronts Alex in the hallway, demanding to know if she has another Denny Duquette situation on her hands. Alex insists that he needs to be that prepared if he's going to be in her O.R. In the heat of the confrontation, she kisses him and pushes him into the nearest room and they start tearing each other's clothes off. Mark sees them emerge from the room afterward and puts two and two together.
He makes a move on Meredith, who turns him down, saying revenge sex is never the answer and he should just be an adult about it. Addison asks Mark out for a drink so they can talk, but he tells her no, he's not the guy for her. He lies and says he slept with someone, so the bet is off.
At lunch, Meredith says she thinks that the penis fish is "instant karma" for cheating. Cristina points out that she's cheated on people and escaped karmic payback and then poses the question to Izzie and George that she can't be the only one. They freeze, then turn the conversation to which wedding cake they prefer.
Everyone leaves the table but George and Izzie, who say it's no big deal that they didn't answer the cheating question because everything is fine. Callie walks up, sees that they're playfully feeding each other cake and keeps going in disgust.
Cristina tries to get Callie's notes but Callie says no. But when Cristina gripes that she's just going to give them to George, who'll only share them with Izzie since they're "like an exclusive little unit," Callie hands the cards over. Callie corners Izzie and says that she can't compete with Izzie, since Izzie is George's best friend. "Give me my husband back," she begs.
Richard successfully removes the penis fish from Jenning. George tries to chat up Izzie and she tells him he's her penis fish: He's latched on and she can't get rid of him, so things are not okay. Meanwhile, Jenning's wife tells George, "The wife always knows." Celeste leaves Larry and it appears that his wife might be leaving him as well.
Richard orders Miranda to go home and stop beating herself up about the one case she got wrong, adding that if she doesn't go home soon, she might not have a family to go back to.Izzie is sadly eating wedding cake samples when Burke asks which one she likes best. He says no one ever tells him anything, so she tells him she slept with a married man and that it was George. He just keeps talking about the cakes, saying how much his wedding day and Cristina mean to him. Cristina is busy studying with Callie's notes when Burke asks her which cake she likes best. She finally picks the same one Izzie did and he seems pleased.
Addison finds Alex studying and volunteers to quiz him. He tells her she's not his girlfriend and that he's busy.
Meredith goes to see Derek at his trailer, apologizing again for the hovering remark. But when she finally notices he's not happy, he tells her he can't get over the fact that when she fell in the water, she didn't swim. Ever since then, he's been trying to breathe for her, he says and he doesn't know if he can keep doing that. She says she should go and he doesn't stop her.