Electrical stimulation of 5-hydroxytryptamine (5-HT) containing cell bodies in the nucleus raphe medianus (NRM) evoked complex responses on most cortical neurones. The predominant response pattern was biphasic, a short latency inhibition being followed by a long latency excitation. Occasional cells showed a third phase, a very long latency weak inhibition. When tryptamine was applied iontophoretically with ejecting currents which did not alter cell firing rate the excitatory effects of NRM stimulation were profoundly reduced. The initial inhibition of cell firing was not altered by tryptamine but some evidence suggested that the long latency inhibition could be potentiated. The results may suggest that tryptamine can modify the neuronal effects of synaptically released 5-hydroxytryptamine.