Cyclosporin A (Cs A), added to the fluid bathing the internal surface of the isolated skin of Rana esculenta, increased short-circuit current (SCC) with a maximal effect at 5 microM. This effect was completely inhibited by amiloride (0.2 mM in the fluid bathing the external surface). By measuring both transepithelial fluxes of 22Na+ across symmetrical parts of the short circuited skin, Cs A was found to increase the net absorption of Na+. Naproxen (10 microM), a cyclooxygenase inhibitor, decreased the stimulation by Cs A of SCC, suggesting that in this stimulation prostaglandins are involved. The Cs A effect on Na+ transport could be caused by an inhibition of a Ca2+/calmodulin-dependent protein phosphatase, i.e. calcineurin, since: a) it is mimicked by another inhibitor of calcineurin, i.e. fenvalerate: b) the action of Cs A and fenvalerate on SCC are decreased by the calmodulin inhibitor W7.