The hypotensive effect of cryptenamine has been reported to be markedly attenuated by adrenalectomy or by treatment with N,N-diisopropyl-N′-isoamyl-N′-diethyl-aminoethylurea (P-286) in atropinized animals. Cryptenamine also appeared to potentiate the response of isoproterenol on β-adrenergic receptors. This present study was conducted to further investigate these two phenomena. Cryptenamine potentiated the response of epinephrine on the β-adrenergic receptors in the intact dog heart, partially blocked the effect of isoproterenol on the isolated guinea pig auricle, and had no effect on the isoproterenol-induced relaxation of the isolated guinea pig tracheal chain. Cryptenamine produced positive inotropic and chronotropic effects on the isolated guinea pig heart and potentiated the inotropic effect of epinephrine and inhibited its chronotropic effects in this preparation. These data suggest that the effects of cryptenamine on β-adrenergic receptors are variable and that either potentiation or inhibition may be observed depending on the effector organ and on the species of animal studied. Cryptenamine also significantly decreased the epinephrine content of the adrenal venous blood while increasing the norepinephrine content suggesting that the drug may inhibit the methylation of norepinephrine in the adrenal medulla.