The sleep electroencephalogram (EEG) was used to assay central effects of pindolol (10 and 30 mg p.o.), a mixed β 1 2 -adrenoceptor/5-hydroxytryptamine (5-HT) 1 A / 1 B receptor blocker, in humans. Compared to placebo, pindolol produced a dose-related suppression of rapid-eye-movement (REM) sleep, including a prolongation of REM latency, and a decrease of REM time and REM density. At the higher dose, it also reduced EEG spectral power during non-REM sleep in portions of the δ, θ, and α frequencies (1.125-5.125 Hz, 7.125-9.625 Hz). By contrast, betaxolol (20 mg p.o.), a selective β 1 -antagonist devoid of serotonergic affinity, affected neither REM sleep nor EEG power. REM sleep is, in part, under the inhibitory control of serotonergic neurons projecting from the dorsal raphe nucleus to pontine cholinergic/cholinoceptive cells. The EEG power spectrum induced by pindolol tended to be opposite to what has previously been reported for ipsapirone, a 5-HT 1 A agonist. Therefore, the present data, tentatively, are consistent with the contention that pindolol inhibits, possibly selectively, somatodendritic 5-HT 1 A autoreceptors in humans and may antagonize self-inhibition of midbrain raphe nuclei 5-HT neurons.