This study examined the effects of nefazodone, trazodone and buspirone on sleep and sleep-related penile tumescence. Trazodone is a sedating antidepressant without anticholinergic properties. Nefazodone is a new antidepressant that is a structural analogue of trazodone but is less sedating. Buspirone is a nonsedating, nonbenzodiazepine anxiolytic with antidepressant properties. Nefazodone was compared to trazodone and buspirone in a double-blind, placebo-controlled crossover study in 12 normal healthy males. Nefazodone increased rapid eye movement (REM) sleep, whereas trazodone and buspirone suppressed REM sleep. The drugs only minimally affected other sleep stages. Trazodone increased total tumescence time by delaying the onset of detumescence; nefazodone increased total tumescence time only insofar as it increased REM sleep; buspirone did not change total tumescence time when compared to placebo. The results support a growing body of data indicating that not all antidepressants suppress REM sleep. The results also are consistent with the interpretation of an earlier study showing that trazodone prolongs penile tumescence during sleep as a result of its alpha-adrenergic blocking properties that suppress detumescence. Nefazodone, with less alpha-adrenergic blocking activity, did not abnormally penile tumescence beyond REM sleep.