Iatrogenic sexual dysfunction has been associated with many pharmacologic agents. The authors report 6 cases of orgasm dysfunction associated with the use of fluorxetine in 77 depressed outpatients. Fluoxetine is a novel antidepressant known to block the reuptake of serotonin with little effect on other neurotransmitter systems. Because fluoxetine has a specific mechanism of action, it serves as a useful model to hypothesize about potential mechanisms of drug-induced sexual dysfunction. The possible effects of serotonin on central, spinal, and peripheral anatomical areas are discussed in relation to drug-induced sexual dysfunction.