Single shock stimulation of the nucleus raphé medianus evoked complex responses from the large majority of neurones tested. These responses consisted of a short-latency (mean 21 msec) inhibition of firing followed by a longer latency (mean 160 msec) increase in firing rate. Occasionally, cells were encountered which exhibited pure inhibitory or pure excitatory responses. Prior treatment with the tryptophan hydroxylase inhibitor rho-chlorophenylalanine reduced the excitatory effects of raphé stimulation but greatly increased the inhibitory effects. Pretreatment with 5,7-dihydroxytryptamine (5,7-DHT), on the other hand, reduced both inhibitory and excitatory effects of raphé stimulation. Methysergide was found to be an effective antagonist of excitatory responses to iontophoretically applied 5-hydroxytryptamine (5-HT) but less effective against depressant responses to either 5-HT or tryptamine. In contrast metergoline consistently antagonized 5-HT and tryptamine-induced depressions but not 5-HT elicited excitations. When tested against stimulation evoked responses of cortical neurones methysergide antagonized the excitatory effects of raphé stimulation but had much less effect on the inhibitory responses, while the reverse held true for metergoline. The present results may be compatible with a mediation of the excitatory effects of stimulation by 5-HT and the inhibitory effects by tryptamine.