The apparent Arrhenius energy of activation (Ea) of the water osmotic permeability (Pcos) of the basolateral plasma cell membrane of isolated rabbit proximal straight tubules has been measured under control conditions and after addition of 2.5 mM of the sulfhydryl reagent, para-chloromercuribenzenesulfonic acid (pCMBS), of mersalyl and of dithiothreitol. Ea (kcal/mol) was 3.2 +/- 1.4 (controls) and 9.2 +/- 2.2 (pCMBS), while Pcos decreased with pCMBS to 0.26 +/- 0.17 of its control value. Mersalyl also decreased Pcos both in vitro and in vivo (using therapeutical doses). These actions of pCMBS and mersalyl were quickly reverted with 5 mM dithiothreitol and prevented by 0.1 M thiourea. Ea for free viscous flow is 4.2 and greater than 10 for non-pore-containing lipid membranes. By analogy with these membranes and with red blood cells, where similar effects of pCMBS on Pos are observed, it is concluded that cell membranes of the proximal tubule are pierced by aqueous pores which are reversibly shut by pCMBS. Part of the action of mercurial diuretics can be explained by their action on Pcos.