The effect of morphine administration on the subsequent stimulation of prolactin (PRL) secretion and the release of dopamine from tuberoinfundibular neurons was examined in this study. The administration of morphine (15 mg/kg s.c.) resulted 4 hr later in suppressed serum PRL concentrations. In addition, the increase in serum PRL concentrations induced by restraint stress was attenuated greatly in rats treated 4 hr earlier with morphine. The morphine-induced attenuation of the PRL response to restraint stress was time-dependent and dose-related. The suppressive effect of morphine on PRL secretion was observed 3 to 6 hr after its administration and at doses of 10 to 20 mg/kg. A single injection of morphine also resulted 4 hr later in an attenuation of the PRL response to a second injection of morphine (7.5 mg/kg); however, the increase in serum PRL concentration produced by alpha-methyltyrosine (250 mg/kg) was unaltered by prior morphine administration. The suppressive effect of morphine on PRL secretion was not observed in rats treated with the opiate antagonist naloxone (2.5 mg/kg). Associated with the delayed suppressive effect of morphine on serum PRL concentrations was a delayed increase in the concentration of dopamine in hypophysial portal plasma and an increase in the turnover of dopamine in the median eminence. The morphine-induced stimulation of the release of dopamine into hypophyseal portal blood was attenuated significantly in animals treated with naltrexone (1 mg/kg). It is concluded that morphine exerts a biphasic effect on both the secretion of PRL and the release of dopamine from tuberoinfundibular neurons.(ABSTRACT TRUNCATED AT 250 WORDS)