Net fluid movement and mucosal 14C-erythritol clearance were measured in ligated colonic loops of the rat in vivo. The diphenolic laxatives, oxyphenisatin and bisacodyl, dose-dependently inhibited net fluid absorption or caused secretion, both increased the 14C-erythritol clearance. Pretreatment with the adenylate cyclase inhibitor, RMI 12 330 A, did not change these results. It is concluded that diphenolic laxatives mainly influence intestinal fluid transport not by stimulation of mucosal adenylate cyclase but rather by augmenting epithelial permeability.