The effects of acute ritanserin treatment on dopamine (DA) and serotonin (5-HT) release and metabolism were studied in tissue and microdialysis samples of the nucleus accumbens in rats. Administration of a moderate dose of ritanserin elicited decreases in DA and 5-HT in tissue with concomitant increases in extracellular fluid. These data show that selective 5-HT2 receptor antagonism modulates DA as well as 5-HT neurotransmission and adds support to the suggestion that 5-HT/DA interactions may be important in the treatment of psychoses.