Studies were performed to determine the effects of phenylephrine in dogs under chloralose as influenced by mechanical buffering of blood pressure, adrenergic blockade produced by injection of phenoxybenzamine, and combination of the mechanical buffering of blood pressure and phenoxybenzamine administration. Chloralose did not interfere with and possibly mildly sensitized the cardioinhibitory response to phenylephrine. Tachyphylaxis did not occur when moderate doses of phenylephrine were injected at intervals of not less than 15 minutes. Either mechanical buffering or administration of phenoxybenzamine partially prevented the pressor response to phenylephrine, and the cardioinhibitory response correspondingly was less. When the increase in blood pressure was prevented entirely by mechanical buffering of blood pressure combined with phenoxybenzamine administration, phenylephrine caused either no change in heart rate or a mild acceleration. It is concluded that the decreases in heart rate which are observed following injection of phenylephrine, in the doses used in this study, are secondary to the adrenergic actions of the compound.