Treatment of rats at night with a non-competitive NMDA receptor antagonist MK-801 (0.025-1 mg/kg, i.p.) produced a dose-dependent decrease in the nocturnal activity of the pineal serotonin N-acetyltransferase (NAT), the rate limiting enzyme in melatonin biosynthesis. A maximal inhibition (by 67-75%) of the enzyme activity was observed after the drug doses of 0.1 mg/kg in female rats, and 1 mg/kg in male animals. The data suggest that the NMDA receptor-mediated glutamatergic neurotransmission is a step necessary for NAT induction (and melatonin biosynthesis) in the mammalian pineal gland.