Although the excitatory amino acid, N-methyl-DE-aspartate (NMA), is generally thought to stimulate LH release, we have previously reported that NMA inhibits LH secretion in the adult ovariectomized (OVX) rhesus monkey. The objectives of this study were: (1) to compare the effect of NMA on LH in the OVX monkey before and after replacement with ovarian steroids, and (2) to evaluate the LH response to NMA in the intact female monkey during three phases of the menstrual cycle. Three hourly injections of NMA (45 mg i.v.) were given to OVX monkeys (OVX; n = 12) and to OVX animals treated for 4 days with estradiol alone (OVX + E; n = 4) or with estradiol plus progesterone (OVX + E/P; n = 5). Replacement with ovarian steroids prevented the NMA-induced decrease in LH: mean ( ± SE) areas under the LH curve (expressed as a percentage of the 3-hour baseline preinjection control) during the 3-hour NMA treatment period were as follows: OVX,-26.6% ± 2.4; OVX + E, +69.6% ± 33.9; OVX + E/P, + 161.5% ± 59.3 (p