The effect of the steroid hormone progesterone on transepithelial sodium transport was measured in confluent monolayers of the A6-cell line from Xenopus kidney. Apical permeabilization with Amphotericin B enabled us to measure the Na+/K+-pump current, and current-fluctuation analysis was used to analyze changes in apical channel density and gating characteristics. Basolateral progesterone (22.2 microM) had a rapid inhibitory effect on the Na+/K+-pump current, and a corresponding decrease in Na+ channel density. The effect occurred within some minutes and took about 50 min to reach a new steady state, in which 45% of the macroscopic current (ISC) was inhibited. Progesterone also inhibits the hypo-osmotic stimulation of Na+ channels which occurs in untreated monolayers. Compared with the known effects of adrenal steroids, our results show a rapid inhibitory action of a steroid hormone on Na+ absorption. The time profile of the progesterone effect suggests, at least in the first minutes, a non-genomic action of progesterone.