The rat alpha 7 neuronal nicotinic acetylcholine receptor was expressed and studied in Xenopus oocytes. The magnitude and reversal potential of instantaneous whole cell currents were examined in solutions containing varying concentrations of either calcium or barium, and in the presence or absence of the intracellular calcium chelator BAPTA. In external barium, application of nicotine elicits an inwardly rectifying response; in calcium the response is larger and has a linear IV relation. Pretreatment of oocytes with BAPTA-AM could not prevent activation of calcium-dependent chloride channels in external Ringer containing calcium. Using an extended GHK equation, the permeability ratio PBa/PNa of the alpha 7 receptor was determined to be about 17. Our results suggest that alpha 7 nicotinic receptors are highly permeable to divalent cations.