The pyrimidine nucleoside, uridine, has been proposed as a potential supplement in the treatment of psychosis based on its ability to reduce haloperidol-induced dopamine release. These experiments investigated the effect of uridine (32 mg/kg, i.p.) coadministered with the neuroleptic haloperidol, on rats engaged in one way conditioned avoidance responding. Uridine itself had no effect on animals' performance, while haloperidol (dose range 0.05-0.4 mg/kg, i.p., 90 min before test session) decreased number of avoidances and increased avoidance and escape latencies in a dose-dependent manner. When coadministered with haloperidol, uridine significantly potentiated the disruption of avoidance and avoidance latency induced by haloperidol. This potentiation was still evident after chronic (27 days) uridine treatment. Importantly, coadministration of uridine did not potentiate haloperidol-induced increase of escape latency. The potentiation of haloperidol-induced disruption of conditioned avoidance responding suggests that uridine coadministration might enhance the antipsychotic action of traditional neuroleptics. This would allow for a reduction in the therapeutic dose of the antipsychotic, thereby reducing side effect frequency.