We have investigated the effects of 17ß estradiol and progesterone on the transepithelial electrical resistance (R_TE) in sheep visceral and parietal pleura. Specimens of intact pleura from adult female sheep were used. The samples were transferred to the laboratory within 30 min from the death of the animal in a Krebs-Ringer solution at 4°C. The pleura was then mounted as a planar sheet in Ussing-type chamber and electrical measurements were made. There was an increase in R_TE in all of the samples examined after addition of 17ß estradiol and progesterone in visceral and parietal pleura. This increase was rapid within 1 min, lasted for about 15 min, returned to the basal level within 30-45 min, and was dose dependent. Tamoxifen, an estrogen receptor antagonist, did not eliminate significantly the effect of 17ß estradiol, furthermore no steroid receptors were identified in cytosolic preparations of visceral and parietal pleura, with ligand binding assays. The estrogen and progesterone induced increase in R_TE was affected by addition of an inhibitor of the nitric oxide synthase in both visceral and parietal pleura. Indeed, previous administration of N-nitro-L-arginine methyl ester (L-NAME) prevented the increase in R_TE by of 17ß estradiol and progesterone. These results suggest that 17ß estradiol and progesterone induce an increase in R_TE in both visceral and parietal pleura and thus alter the transepithelial permeability. The effect of steroids may be accounted by rapid release of nitric oxide in pleura.