Homovanillic acid (HVA) levels were determined by high performance liquid chromatography with electrochemical detection in the striatum and prefrontal cortex of rats that had received single or repeated injections of various doses of haloperidol. Haloperidol increased the HVA concentrations in both brain regions after both acute and chronic treatment with doses of 0.01-1 mg/kg. The increase in the HVA concentrations in the striatum was blunted after repeated haloperidol injections with doses of 0.5-1 mg/kg, suggesting that haloperidol pretreatment results in a decreased responsiveness to the drug at high doses (tolerance). Tolerance also developed to the effect of long-term haloperidol treatment on the HVA concentrations in the prefrontal cortex at the highest dose used (1 mg/kg). This suggests that the differences in the development of tolerance between the striatum and prefrontal cortex are not qualitative but quantitative. However, repeated haloperidol injections at doses of 0.01-0.05 mg/kg enhanced the increase in HVA concentrations. This suggests that tolerance does not develop after chronic haloperidol treatment with low doses. Decreased HVA concentrations were also found after withdrawal from chronic haloperidol treatment (rebound decrease). However, this rebound decrease was much smaller than the decrease in response of the HVA concentrations to repeated haloperidol injections, suggesting that different mechanisms are involved.