In the rhesus macaque, activation of NMDA receptors can markedly stimulate LH secretion. However, it is unclear whether these receptors are physiologically involved in the generation of the preovulatory LH surge; if so, their pharmacological blockade ought to perturb the timing of this surge or attenuate its magnitude and duration. In the present study ovariectomized rhesus macaques were given a s.c. injection of estradiol benzoate (EB; 42 fg/kg BW) to induce a preovulatory-like progression of endocrine events. For the next 72 hours, blood samples were collected remotely from a vascular catheter at 4-hour intervals and assayed for estradiol, LH, cortisol and melatonin. As expected, the EB treatment raised plasma estradiol concentration to ~300 ng/ml and this elevation was maintained for at least 24 hours. A plasma LH peak of preovulatory magnitude (i.e. >300 ng/ml) occurred 48 hours after the EB injection and lasted for ~24 hours. In a second experiment, animals received an identical injection of EB but this was followed immediately by an i.v. injection of MK-801 (1 mg/kg BW), a non-competitive NMDA antagonist; a second injection of MK-801 was administered 24 hours later. In addition, the animals received four i.v. injections of CGP43487 (1 mg/kg BW), a competitive NMDA antagonist, once every 12 hours beginning immediately after the EB injection. As expected, plasma cortisol concentrations doubled during the course of the NMDA receptor antagonism but the circadian pattern of melatonin secretion was not affected. Moreover, plasma LH concentrations showed a surge, which in terms of its timing, magnitude and duration was identical to that observed in the control experiment. The failure of pharmacological doses of NMDA receptor antagonists to influence the estrogen-induced LH surge suggests that these receptors are unlikely to play a significant role in triggering ovulation in primates.