The main goal of this study was to investigate effects of typical (haloperidol) and atypical (risperidone) antipsychotic drugs on brain regional neuropeptide Y (NPY)-like immunoreactivity (-LI) tissue concentrations and on release of NPY-LI in freely moving rats. An additional aim was to explore the effect of d-amphetamine on NPY-LI release following pretreatment with typical and atypical antipsychotics. During a 4-week period, male Wistar rats were fed chow to which vehicle, risperidone (1.15 mg/100 g food or 2.3 mg/100 g food), or haloperidol (1.15 mg/100 g food) were added. In one series of experiments, the animals were sacrificed on day 30 with focused microwave irradiation, the brain regions dissected and extracted for radioimmunoassay of NPY-LI. In another experimental series, probes were inserted into the ventral striatum. The perfusates were collected at 60-min intervals; NPY-LI was determined by radioimmunoassay. Haloperidol significantly increased NPY-LI in hypothalamus and the occipital cortex. In contrast, haloperidol decreased tissue levels of NPY-LI in striatum. Moreover, haloperidol and risperidone also significantly decreased extracellular NPY-LI concentrations in the ventral striatum. d-amphetamine (1.5 mg/kg) significantly increased extracellular NPY-LI in the vehicle group. Both haloperidol and risperidone pretreatments abolished the effect of d-amphetamine. The results show that d-amphetamine as well as haloperidol and risperidone selectively and specifically affect NPY-LI concentrations in brain tissue and microdialysates and that the effect of d-amphetamine is abolished by both typical and atypical antipsychotics.