The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O(2) fraction = 1.0) conditions. At each step, alveolar-to-arterial Po(2) difference (A-aDo(2)) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo(2) was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.