Abnormal polysomnographic (PSG) features, most notably increased electromyographic (EMG) tone and eye movements during non-REM sleep have been observed during sleep in fluoxetine-treated depressed patients. However, the relationship between these PSG features and sleep disruption is unclear. Nine depressed patients treated with 10 to 80 mg of fluoxetine and six unmedicated, depressed patients were studied polysomnographically on two consecutive nights during which sleep parameters, transient arousals, and eye movements were measured. The fluoxetine group experienced a lower-average sleep efficiency index (SEI) and significantly more eye movements and arousals during non-REM sleep than the control group. Eye movement and arousal counts were significantly correlated. In addition, clinically significant periodic limb movement disorder (PLMD) was observed in 44% of the fluoxetine-treated group versus none of the control group. We conclude that a higher incidence of PLMD and frequent transient arousals associated with eye movements may be responsible in part for the complaint of insomnia made by patients treated with fluoxetine.