We have previously suggested that several intercellular messengers activate their receptors via reductive activation. Adenylate cyclase activation involves exposure of a sulfhydryl group. The dopamine D1 receptor activates this enzyme. Because sulfhydryl exposure could be secondary to reduction of a disulfide group we evaluated dopaminergic D1 agonists and antagonists as reducing agents. The agonists were found to be reducing agents and the antagonists were inactive. These results are consistent with the concept that dopaminergic D1 agonists activate adenylate cyclase via reductive activation.