The primary objective of this study was to determine the LH response to an excitatory amino acid agonist, N-methyl-D, L-aspartate (NMA) in the seasonally anestrous ewe. In experiment 1, 3 i.v. injections of NMA were given; doses of 0.5, 1.5 and 4.5 mg/kg BW were tested. LH response to NMA depended on the dose. There was little response to the lowest dose. All animals responded to the first injection of the intermediate and the highest doses (mean pulse amplitude: 9.2 +/- 0.4 and 6.8 +/- 1.2 ng ml, respectively). The responses to the second or third injections of both doses were variable and were either absent or reduced compared to that of the first. In experiments 2 and 3, ewes were given 3 injections of normal saline (NS) followed by 3 injections of NMA (1.25 and 4.5 mg/kg BW, respectively) at 2 hr intervals. The last injection of NMA was followed 2 hr later by an injection of GnRH (3.0 ng/kg BW). In experiment 2, the first NMA injection induced an immediate LH pulse (mean pulse amplitude: 8.0 +/- 1.6 ng/ml) in all ewes, however, the second and third injections induced LH pulses in only 25% and 75% (mean pulse amplitude: 2.2 and 2.4 +/- 0.6 ng/ml) of the ewes, respectively. In experiment 3, NMA increased mean LH release (P less than 0.05) after all injections, but responsiveness to the third injection was reduced in some ewes. GnRH injections induced LH release in all ewes in experiments 2 and 3 (mean pulse amplitude: 6.9 +/- 1.8 and 6.4 +/- 2.2 ng/ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)