The effects of a novel antipsychotic agent, 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2 (1H)-quinolinone (OPC-14597, generic name aripiprazole), on prolactin (PRL) release from isolated rat anterior pituitary slices and on the serum PRL levels were investigated in male rats. In in vitro experiments on the isolated anterior pituitary, the spontaneous PRL release was decreased by talipexole, a dopamine D2 receptor full agonist, in a dose-dependent manner to 36% of the basal release, and the decrease was antagonized by haloperidol, a D2 receptor antagonist. OPC-14597 also decreased the release of PRL at the same concentration range with a maximal decrease to 78%, the potency being weaker than that of talipexole. The decrease in PRL release induced by OPC-14597 was completely antagonized by haloperidol. Moreover, OPC-14597 antagonized the inhibition of PRL release induced by talipexole. In in vivo experiments, haloperidol increased the serum PRL levels to 8 times the basal PRL level, whereas talipexole decreased the levels to 49% of the basal level. OPC-14597 increased the serum PRL levels by 2-fold and also antagonized the talipexole-induced decrease. The hyperprolactinemia induced by estrogen, which was inhibited by talipexole but enhanced by haloperidol, was enhanced by OPC-14597, whereas the hyperprolactinemia induced by reserpine, which was inhibited by talipexole but elevated by haloperidol, was inhibited by OPC-14597. In addition, the OPC-14597-induced inhibition was antagonized by haloperidol. These results suggest that OPC-14597 has a mixed agonist/antagonist profile at D2 receptors on lactotroph cells and thereby exerts either an antagonistic or an agonistic action, depending on the preexisting tone of the dopaminergic neuronal activities.