The aim of this study was to elucidate the effects of N-methyl-D-aspartic acid (NMDA) receptor stimulation on the release of several hormones known to be activated during stress. The experiments were performed in conscious freely moving cannulated rats. Systemic administration of N-methyl-D,L-aspartic acid (NMA) and of NMDA in low doses (2.5-10 mg/kg i.p.) was found to induce a dose-related stimulation of adrenocorticotropin (ACTH) release. NMA-induced ACTH release was reduced by administration of an NMDA receptor antagonist (D,L-2-amino-5-phosphonovaleric acid). NMDA was much more potent in activating ACTH release than the racemic form of the amino acid, NMA. In the dose range used, both NMA and NMDA failed to influence prolactin release. With the exception of a small increase in epinephrine concentration in response to the highest dose of NMDA (10 mg/kg), no changes in plasma catecholamines were observed. The data indicate that NMA and NMDA administered in low doses trigger ACTH release without induction of a nonspecific stress response.