The electrophysiological responsiveness of nigrostriatal dopamine (DA) neurons to dorsal raphe stimulation and to systemic administration of serotonin (5-HT) selective compounds was examined in chloral hydrate-anesthetized rats. Electrical stimulation of the dorsal raphe selectively inhibited the firing rate of slowly firing (less than 4 spikes/sec) DA neurons. The 5-HT-1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methoxy-N,N-dimethyltryptamine preferentially increased the firing rate of slowly firing DA neurons, but did not alter the responsiveness of these cells to quinpirole-induced inhibition of firing rate. This increase in firing rate was not observed following depletion of brain 5-HT by the neurotoxin 5,7-dihydroxytryptamine. The 5-HT-1B agonists trifluoromethylphenylpiperazine and M-chlorophenylpiperazine had only weak inhibitory effects on the firing rates of DA neurons, and also failed to alter the responsiveness of DA neurons to quinpirole-induced inhibition. Depletion of brain 5-HT (greater than 80%) by either para-chlorophenylalanine or 5,7-dihydroxytryptamine eliminated the rate-dependent nature of quinpirole-induced inhibition of nigrostriatal DA neurons, while having limited effects on the basal electrophysiological activity of these cells. These data suggest that 5-HT systems exert subtle influences on the activity and pharmacological responsiveness of nigrostriatal DA neurons.