A sexually transmitted disease breaks out and affects several members of the hospital staff. Chief Webber promptly calls a meeting. Meanwhile, the chief reluctantly tells Dr. Derek Shepherd about his own medical concerns. Izzie and Cristina worry about a patient's wife and daughter who can't agree on his care. Burke treats his college buddy Bill, whose medical diagnosis raises some questions regarding his wife's actions. Then just as Meredith and Derek grow more intimate, a surprise is revealed.

As Cristina tries to recover, she proves to be a very difficult patient, and a visit from her mother doesn't improve her demeanor any. And Meredith's mother, Dr. Ellis Grey, has the hospital staff running in circles.

Dorie Russell is waiting for quintuplets, all 5 girls. Her husband seems more concerned than she is but she is set to bring her babies to their term of 36 weeks. All the departments are on call for the quintuplets as three of them have developped problems of different kinds. Meredith last night's stand shows up at the hospital with priapism and they need to call Derek Sheperd for a consult which puts Meredith in a very embarassing position. Alex and Derek must take care of a patient who has a tumor inducing thirst as a side effect. On the love side, Alex and Izzie are having some slight sexual problems, while Meredith goes on adding one night stands and Cristina is thrown off course by being "keyed."

Meredith and George are experiencing morning-after tension at home and at work and it has the rest of the doctors wondering what's up. Derek and Addison are experiencing their own version of morning-after tension as a result of Mark's visit to Seattle. Bailey, returning the favor that was done for her during the Code Black situation, must treat Addison for a specific feminine problem. Izzie and Alex are making headway in their relationship until Denny Duquette comes back. Soon Alex is not-so-oddly jealous of the attention Izzie is showing to Denny. Someone finds comfort in confiding in a patient who is going through an ordeal of his own. Burke deals with a patient and gets to observe the patient's unstable relationship with his fiancée.