Bilateral intracerebroventricular injection of D-alanine (200-600 micrograms/rat) antagonized the ability of methamphetamine (1.0 mg/kg s.c.) to induce locomotor stimulation in the rat. In contrast, L-alanine (600 micrograms/rat) failed to affect the behavioral change induced by methamphetamine. The stereoselectivity parallels the potency of these amino acids as agonists for the strychnine-insensitive glycine binding site within the NMDA receptor complex. These results support the view that reduced excitatory amino acidergic neurotransmission may be involved in methamphetamine-induced hyperactivity.