The effects of sodium salicylate on the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), 2-hydroxyoctadecanoic acid, 9-anthroate (2-AS), 12-hydroxyoctadecanoic acid, 9-anthroate (12-AS), 8-anilino-1-naphthalenesulfonic acid (ANS) and 2',4',5',7'-tetrabromo-5-maleimidofluorescein, disodium salt (EM), with which rat small intestinal brush border membrane vesicles were labeled, were examined. Salicylate ion decreased the fluorescence polarization of ANS and EM in these vesicles, however, it had no influence on the fluorescence polarization of DPH, 2-AS and 12-AS-labeled vesicles. It also released trapped 6-carboxyfluorescein (3',6'-dihydroxy-3-oxospiro-[phthalan-1,9'-xanthene]-6-carbo xylic acid) (CF) from the vesicles, but caused no leakage of trapped CF from liposomes. These results indicate that salicylate ion increases the plasma membrane permeability by effecting the plasma membrane proteins rather than directly interacting with the membrane lipids. The action of salicylate ion on these vesicles could possibly promote nonabsorbable drug absorption in vivo.