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Phenylpropanolamine is found in a number of over-the-counter preparations commonly used for appetite control or as a cold remedy. Even though widely used, some questions still exist as to its effect on the cardiovascular system of man. Both anesthetized and unanesthetized adult beagle dogs were used in this study. In the unanesthetized conditioned dog, blood pressure and heart rate were measured using an inflatable tail cuff. In the first group, consisting of 12 dogs, phenylpropanolamine was given (0.0, 3.1, 6.25 and 12.5 mg/kg) via a stomach tube and the animals were followed for 300 minutes. Each dose of phenylpropanolamine was given to 4 groups made up of 3 dogs each. It produced dose-dependent increases in blood pressure and decreases of heart rate. Maximum changes were noted at 30 to 60 minutes, lasting for 3 to 5 hours. A second group of 9 unanesthetized dogs was given repeated oral doses of phenylpropanolamine (3 groups of 3 animals each). Doses of 3 mg/kg and 6 mg/kg, given orally, produced approximately the same increase in blood pressure and decrease of heart rate as previously observed. At 6 hours, these same doses of phenylpropanolamine produced little or no change in either parameter. At 24 hours after the first dose, however, the dogs responded in much the same manner as with the first administration of phenylpropanolamine. Control dogs given water did not exhibit any degree of tachyphylaxis. Dogs anesthetized with Na pentobarbital were given oral and intravenous doses of phenylpropanolamine (0.0-25 mg/kg). The overall response was like that observed in the unanesthetized preparation with the important exception that low doses (0.1-3 mg/kg) produced significant increases in both heart rate and blood pressure, while higher doses (6-25 mg/kg) resulted in a lesser overall effect. Six anesthetized animals were used to study the effects of phenylpropanolamine and norepinephrine on the cardiovascular function. Both the increase in blood pressure and left ventricular force of contraction, produced by the first dose of phenylpropanolamine, were markedly reduced or absent with the second administration of the drug. In addition, the classic blood pressure response to norepinephrine was likewise increased by prior administration of phenylpropanolamine.(ABSTRACT TRUNCATED AT 400 WORDS)