The effects of doxepin hydrochloride (Adapin) on sleep and depression were evaluated in nine depressed patients with documented sleep difficulties. All subjects were screened for depression on the Hamilton Psychiatric Rating Scale. Sleep disturbance was measured by all-night polysomnography. Doxepin in doses of 75 and 150 mg/day significantly improved sleep efficiency, as evidenced by decreased sleep latency and increased total sleep time. After 2 weeks of treatment, REM latency and percent REM time were dramatically changed. Maximal improvement in depression occurred after 2 weeks of doxepin therapy and at the 150 mg dose.