We studied the effect of MK-801, a potent non-competitive NMDA receptor antagonist, on the micturition reflex in anesthetized rats. Pretreatment with MK-801 (0.1-1 mg/kg i.v.) dose dependently increased the bladder capacity and reduced the micturition contraction. The ability of MK-801 to inhibit bladder voiding was confirmed in additional experiments in which the compound (30-50 micrograms/kg i.v.) transiently suppressed established bladder voiding produced by continuous bladder filling. MK-801 (1 microM) did not affect nerve-mediated contractions of the rat bladder or inhibit the response to capsaicin. These findings provide pharmacological evidence for an involvement of NMDA receptors in the micturition reflex pathways.