Pineal beta1-adrenergic receptors are involved in the regulation of melatonin secretion. The involvement of beta1-adrenergic receptors has been demonstrated by the ability of acute administration of beta-antagonists to suppress the nocturnal rise of circulating melatonin and its urinary metabolite 6-sulphatoxymelatonin (aMT6s). The present study was undertaken to examine the relationship between increasing doses of atenolol and nocturnal plasma melatonin concentrations. Six healthy subjects participated in the study for a period of 5 weeks. Subjects were administered placebo, 12.5, 25, 37.5, and 50 mg doses of atenolol in a randomized single blind design. Each dose was separated by a 1 week washout period. Blood samples were collected at regular intervals from 19.00 hr to 06.00 hr. Repeated measures analysis of variance showed a dose-dependent decrease in plasma melatonin concentrations (P<0.01). A Student Newman-Keuls post hoc test indicated significant differences between placebo and all doses of atenolol (P<0.05). The results demonstrate a dose-dependent relationship between beta1-receptor blockade and suppression of nocturnal plasma melatonin in humans.