Rats were prepared with chronic bipolar electrodes aimed at either the caudate-putamen or lateral hypothalamus and those displaying consistent self-stimulation were given additional training at half-maximal current intensities. All subjects received an intragastric injection of para-chlorophenylalanine (400 mg/kg) and self-stimulation tests continued until pre-injection rates were re-established. Responding in both brain areas was suppressed 24 h after drug treatment. The next day, self-stimulation rates in the hypothalamus increased to 115% of pre-drug levels reaching a level of 180% by the third day of post-drug testing. In contrast, self-stimulation of sites in the neostriatum continued to decline, with minimal levels reaching 48% of control on the fourth post-drug day. Self-stimulation rates in both groups had returned to control levels by post-drug day 6. These data indicate that the role of serotonergic mechanisms in brain stimulation is locus specific, and that the specific nature of this role may be determined by interaction with other neurochemical systems. The possible interaction between dopaminergic and serotinergic mechanisms in the neostriatum is discussed as a model of self-stimulation in this region of the brain.