We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by a) 2-[125I]iodomelatonin binding (Kd: 75.7 ± 6.9 pM, Bmax: 2.6 ± 0.4 fmoles/mg protein), b) cDNA identification and c) melatonin inhibition of ACTH- and CRH-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma estradiol during gestation and on plasma cortisol concentration in the 4-6 days old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma estradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal estradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light/dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation.