The hyperpolarizations in response to ATP and adenosine in the guinea-pig taenia coli, measured by the sucrose-gap technique at room temperature, were compared in solutions of modified ionic composition. ATP hyperpolarization was increased in low chloride and in low potassium, but was reduced to 12% of control in calcium-free solution on second application of the agonist. The response to adenosine, however, was decreased in low chloride, unchanged in low potassium and was 45% of control in calcium-free solution. The different mechanisms for ATP and adenosine hyperpolarization provide evidence for the presence of separate receptors.