Potassium-evoked 3H-serotonin (5-HT) release from rat cerebrocortical synaptosomes was performed after peripheral inoculation with fixed rabies virus CVS (challenge virus strain). At the onset of clinical symptoms, the rats were sacrificed, synaptosomes were prepared from dissected cortices and assayed for K+ evoked 5-HT release. The results show a decrease in evoked 5-HT release from virus-infected synaptosomes. Alterations in serotoninergic transmission in rabies virus infected brain cortex indicate a possible involvement in the triggering of pathogenetic mechanisms relating to the clinicopathological manifestations of the viral disease.