A single s.c. injection of penfluridol (3 mg/kg) to rats elevated serum concentrations of prolactin for more than 96 h whereas it increased striatal concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and inhibited apomorphine-induced circling behavior for less than 48 h. The dose of penfluridol needed to elevate serum concentrations of prolactin (0.1 mg/kg) was less than that required to elevate striatal concentrations of DOPAC (1 mg/kg) or inhibit apomorphine-induced circling (3 mg/kg). Furthermore, the penfluridol-induced increase of striatal DOPAC was more susceptible to reversal by apomorphine than was the increase of serum prolactin concentrations. These results suggest that the dopamine receptors in the pituitary, which are normally activated by dopamine released from tuberoinfundibular neurons, are more sensitive to the blocking actions of systemically administered penfluridol than are dopamine receptors in the striatum.