Cadmium, 10−3 mol/l on the mucosal or 10−5 mol/l on the serosal side of the toad urinary bladder, inhibits the hydro-osmotic effect of vasopressin. This inhibition is irreversible. The osmotic transfer of water in the absence of vasopressin was unaffected by the presence of the Cd2+. The hydro-osmotic response to cyclic AMP was also reduced by the Cd2+, but the response due to hypertonicity of the serosal bathing solution was unaffected. The short-circuit current (reflecting active transmural Na+ transport) was inhibited by 10−3 mol Cd2+/1 on the serosa, but was increased by 10−3 mol/l at the mucosa or 10−4 mol/l at the serosa. The natriferic response of the bladder to vasopressin was unaffected when Cd2+ was present under conditions that inhibited the hydro-osmotic response, further emphasizing that separate effector mechanisms may be involved for each effect.