Ethanol, 50 mM, in vitro inhibited the release of [3H]dopamine ([3H]DA) induced by depolarisation with 40 mM K+ from slices of corpus striatum of the rat. In contrast, the release of [3H]DA induced by the Ca2+ ionophore (A23187) was enhanced by the presence of ethanol in vitro. When similar preparations were obtained from brains of rats which had received ethanol in vivo chronically by inhalation for 5-7 days the characteristics of release of [3H]DA were altered. Thus, the inhibitory effect of ethanol in vitro on release induced by K+-depolarisation was lost, as was the enhancing effect of ethanol on the release induced by A23187. When release of [3H]DA was studied in the absence of added ethanol the fraction of stored 3H released either by K+-depolarisation or by A23187 was increased in the preparations from animals which had received ethanol in vivo. Similar changes in release induced by A23187, though of lesser magnitude, could be seen in rats which had received ethanol acutely (3 g kg-1 i.p.; 30 min). An even greater fraction of [3H]DA was released by A23187 in preparations from rats which had been made physically dependent on ethanol. These changes in the release characteristics of [3H]DA were still apparent in animals undergoing a physical syndrome of withdrawal from ethanol. The results are discussed in relation to the cellular basis for the development of tolerance to and dependence on ethanol.