Monensin, a highly selective sodium ionophore, inhibits vasopressin‐stimulated water flow in toad urinary bladder pretreated with naproxen, an inhibitor of prostaglandin synthesis. Inhibition is partially dependent on the presence of sodium in the serosal medium, but not on serosal calcium. We have found that monensin does not inhibit water flow generated by forskolin, cyclic AMP, or isobutyl methyl xanthine (MIX); indeed, an enhancement of water flow was seen following cAMP and MIX, as well as following 0.2 μM forskolin. Our findings suggest that monensin uncouples the vasopressin‐receptor‐G protein‐adenylate cyclase sequence at some early step, by a mechanism that remains unknown, but that may directly or indirectlyinvolve intracellula