In view of the report that Mn2+ stimulates sodium transport in the toad bladder but inhibits the effect of vasopressin on both water flow and sodium transport, the effects of this ion on adenyl cyclase from mucosal epithelial cells of toad bladder were investigated. Mn2+ was found to inhibit activation of adenyl cyclase by arginine vasopressin in the presence of Mg2+ and had no effect on activation of the enzyme by sodium fluoride. This is in marked contrast to the effects of Mn2+ on hormonal activation of adenyl cyclase from other tissues in which no inhibitory effects are seen and in which Mn2+ can replace Mg2+ in the reaction mixture. It is concluded that stimulation of sodium transport by Mn2+ is unlikely to be explainable by adenyl cyclase activation and that Mn2+ is not useful in the differentiation of the two forms of adenyl cyclase which are thought to be required for mediation of water flow and sodium transport stimulation by vasopressin.