To determine whether ipsapirone, a 5-HT1A agonist, differentially suppresses REM sleep in depressed patients compared with normal controls, we administered placebo, ipsapirone 10 mg, or ipsapirone 20 mg in a double-blind, random order before bedtime in 18 unmedicated patients with depression and 16 age-matched, gender-matched normal controls. Compared to placebo, ipsapirone affected REM sleep measures equally in depressed patients and controls as follows: (1) increased REM latency; (2) reduced total REM percent, REM time, and REM density; and (3) delayed the onset of REM sleep. In addition, ipsapirone had similar effects in patients and controls in other sleep measures: (1) reduced total sleep time; (2) delayed sleep onset time; and (3) increased sleep latency, stage 1%, stage 2%, the amount of stage 3 & 4 sleep in the first non-REM period, and wake time after sleep onset. The study does not support the hypothesis that downregulated 5-HT1A receptors mediate the pathophysiology or sleep disturbances of depression, although further studies are needed as these patients did not differ from controls in baseline sleep measures.