Melatonin administered to female hamsters kept under light:dark cycles of 14:10 (in hours) normally suppresses reproductive processes only if the indoleamine is administered later than 6.5 h after the beginning of the photoperiod. In the present study, we investigated the influence of morning (11.00h) injections of melatonin on the reproductive inhibitory effects of afternoon (17.00 h) melatonin injections. Adult female hamsters were exposed to light daily from 06.00 to 20.00 h. The animals were divided into the following experimental groups: group 1, injected with vehicle at both 11.00 and 17.00 h; group 2, injected with vehicle at 11.00 h and 25 μg melatonin at 17.00 h; group 3, injected with 1 mg melatonin at 11.00 h and 25 μg melatonin at 17.00 h; group 4, injected with 1 mg melatonin at 11.00 h and vehicle at 17.00 h. Control animals injected with vehicle at both 11.00 and 17.00 h had normal 4-day estrous cycles throughout the 8 weeks of the experiment. 100% of the animals injected with vehicle in the morning and melatonin in the afternoon became acyclic within 7 weeks. However, if the afternoon injections of melatonin were preceded by morning injections of the indoleamine, the animals continued to exhibit normal estrous cycles. Also, hamsters injected with melatonin at 11.00 h and vehicle at 15.00 h had normal estrous cycles throughout the study. At the conclusion of the experiment, the uterine weights and plasma prolactin levels in the animals that received vehicle at 11.00 h and melatonin at 17.00 h were depressed compared to those in the vehicle-vehicle injected controls. Again, the morning injections of melatonin prevented the afternoon injections of melatonin from decreasing either the uterine weights or the plasma prolactin levels. It is concluded that the morning injections of melatonin either down-regulated the melatonin receptors or decreased their number and thereby rendered afternoon injections of melatonin incapable of inhibiting reproductive processes.