The physiological and morphological response of toad urinary bladder was examined during mucosal exposure of LiCl both with and without vasopressin (VP). With 20 or 100 mU/ml of VP in the serosal bath there was a decrease in Jv between the first and second VP stimulation in LiCl-treated bladders (VP20, -14 +/- 6%; VP100, -16 +/- 5%) that was not different from that observed without LiCl (VP20, -8 +/- 3%, P = NS). However, with 1 mU/ml of VP, a significant decrease in Jv was evident in LiCl-treated (-30 +/- 10%) versus control sacs (+6 +/- 8%; P less than 0.02). At all VP concentrations tested, a significant decrease in SCC and PD was observed between the first stimulation without LiCl and the second stimulation with LiCl. Both osmotic (Pf) and diffusional water permeability (Pd) were increased significantly with 11 mM LiCl only, while neither basal nor VP-stimulated urea permeability (Pu) was affected. Morphological changes paralleled the physiological alterations induced by LiCl. These data demonstrate that LiCl interferes with the osmotic response of the toad bladder to low concentrations of VP, and increases both Pf and Pd while leaving Pu unaffected. These findings coupled with the cell swelling and intracellular vacuolization suggest the presence of a defect in transepithelial water movement somewhere beyond the apical membrane of the granular cell exposed to LiCl.