In vitro receptor ligand binding studies in the rat showed that remoxipride displaced different radioligands at the dopamine D2, but not the D1 receptor. Remoxipride did not block dopamine-stimulated adenylate cyclase activity in vitro suggesting that it did not directly interact with the dopamine D1 receptor. Like other antipsychotic compounds, it increased dopamine turnover in the dopamine-rich areas of the brain. It showed no affinity for a wide range of neurotransmitter receptors, with the exception of the opiate sigma receptor. The affinity of remoxipride for the D2 receptor was low in vitro, while in vivo, the affinity was relatively high. Remoxipride was far more potent in preventing [3H]raclopride-binding than [3H]spiperone-binding to the D2 receptor in vivo. When the D2 receptor was labelled with [3H]spiperone, remoxipride was shown to exert a preferential blockade of this binding in extrastriatal areas of the brain (for example, olfactory tubercle, septum, substantia nigra) in vivo. After the injection of high doses of remoxipride most if not all drug in the brain was identified as authentic remoxipride. After injection of [3H]remoxipride in smaller and larger doses, radioactivity was detected in all areas of brain examined, including cerebellum and neocortex. Most of the remoxipride-derived radioactivity was found in the choroid plexus and circumventricular organs, while smaller amounts were recovered in the striatum, olfactory tubercle, and substantia nigra. Taken together, these findings suggest that remoxipride acts at both the central D2 and sigma receptors and that its affinity for the D2 receptor is relatively low in vitro. A regional preference for D2 receptors can be observed in vivo depending upon the radioligand used.