A 24-h rhythm has been demonstrated in fetal and maternal melatonin plasma concentrations in pregnant sheep in the last third of gestation. Melatonin in the maternal circulation can cross the placenta and is the major source of melatonin in the fetal circulation. Melatonin has been postulated to act as a prostaglandin (PG) synthetase inhibitor in the uterus. PG synthetase inhibitors decrease myometrial contractility. To assess transplacental passage of melatonin and potential influences of melatonin on uterine contractility, we infused melatonin continuously into the maternal jugular vein in seven pregnant sheep at 138-142 days gestation (term in our instrumented animals is 147 days gestation) at three infusion rates for successive 1-h periods during the late morning to late afternoon. There was no change in the total time during which the myometrium was active, as indicated by myometrial electromyographic activity or the myometrial contracture frequency during the 3 h before and after melatonin infusions and for each hour of the infusions. The MCR for melatonin in the ewe was 4128 +/- 410 ml/min (mean +/- SE; n = 7; weight, 50-70 kg). The resting maternal to fetal melatonin concentration ratio was 0.8; this ratio was maintained at 2.28 during melatonin infusion to the ewe at a wide range of maternal melatonin concentrations. Melatonin concentrations in the range of 3-200 times normal had no effect on the maternal plasma PGF2 alpha metabolite concentration, but caused a 40.4% fall in fetal plasma PGE2 (P less than 0.05). We conclude that changes in maternal and fetal plasma melatonin concentrations within the physiological range observed throughout the day do not alter myometrial contractility, but do alter fetal PGs.