Abstract Recent studies have shown that epinephrine (E), norepinephrine (NE), and isoproterenol (I) cause substantial pulmonary shunting. This study was undertaken to determine the role of alpha (pulmonary vasoconstriction) and beta (pulmonary vasodilatation) adrenergic stimulation in the pathogenesis of pulmonary insufficiency. Forty-three mechanically ventilated, anesthetized dogs received infusions of E, alpha and beta stimulant; NE, a relatively pure alpha stimulant; I, a relatively pure beta stimulant; and dextran (D), a drug with no known adrenergic activity. The cardiac output and shunt measurements were determined simultaneously in the control period and four times during a 1 hour infusion. The quadratic equation of best fit was determined for each group for the relationship between the cardiac output and the shunt over a wide range of cardiac outputs, and statistical comparisons were made between all groups of the shunt at the same cardiac output. In all groups an increase in cardiac output was associated with an increase in the shunt, but the magnitude of the increase in the shunt differed significantly with each drug over the entire range, being smallest with D and becoming progressively larger with I, E, and NE, respectively. It is concluded that an increase in the pulmonary blood flow causes an increase in the pulmonary shunt, but that the magnitude of the increase is dependent on the specific pulmonary microcirculatory effects of each drug.