In this paper, we describe the effects of both acute and chronic ethanol exposure on voltage-activated calcium channels in undifferentiated pheochromocytoma (PC12) cells. Calcium uptake and calcium mediated release studies have shown that calcium channels in these cells are sensitive to ethanol (Messing et al., 1986, Rabe and Weight, 1988, Koski et al., 1991 and Grant et al. in press). Using whole-cell patch clamp techniques, we show that the electrical properties of the channels are very sensitive to acute ethanol. Calcium currents were significantly inhibited by 25 mM acute ethanol and this effect was reversible. In contrast to the reduction of current seen with acute ethanol exposure, chronic ethanol exposure of the cells resulted in a significant increase in calcium current. Examination of whole-cell calcium currents suggested the development of tolerance to ethanol in PC12 cells. Currents evoked from cells exposed to chronic ethanol were inhibited less by acute ethanol than currents from cells not exposed to chronic ethanol. Collectively, these data demonstrate that calcium channels in PC12 cells are sensitive targets for both acute and chronic ethanol.