The intracerebroventricular administration of morphine to ovariectomized rats resulted in a marked decrease in the concentration of dopamine in plasma of hypophysial portal blood. A 90% reduction in the rate of release of hypothalamic dopamine into hypophysial portal blood occurred during the 60 min following the intraventricular administration of 60 ng of morphine sulfate. A dose-related decrease in the rate of release of dopamine into the portal vasculature was observed between 7.5 ng and 60 ng of morphine sulfate. Regardless of the quantity of morphine sulfate (1-500 ng) given to the animals, the concentrations of norepinephrine and epinephrine in hypophysial portal plasma and femoral arterial plasma remained unchanged. The efficacy of morphine on the release of dopamine into hypophysial portal blood was not associated with an equal efficacy of the drug on the synthesis of dopamine in tuberoinfundibular neurons, as evaluated by the accumulation of dihydroxyphenylalanine (DOPA) in the median eminence of rats given 3-hydroxybenzylhydrazine (NSD 1015). No effect of morphine was observed on DOPA accumulation in the median eminence of NSD-treated rats that had received 50 ng of morphine sulfate intracerebroventricularly, and only a 50% reduction was observed in the accumulation of DOPA in the median eminence of rats given 500 ng of morphine sulfate. These findings are supportive of the view that morphine inhibits both the release and synthesis of dopamine but is more effective in inhibiting the release than synthesis of dopamine.