The authors investigated the effects of treatment on ventricular performance when cardiac output (CO) was reduced significantly because of an acute increase in pulmonary vascular resistance (PVR). In eight anesthetized, ventilated dogs, the effects of volume expansion (100 ml 6% dextran) on ventricular performance were determined before and after PVR was elevated. Resistance was increased by microembolization of the pulmonary vascular bed with glass beads (80-100 microns). When PVR was normal, volume expansion increased (P less than 0.05) stroke volume (SV) and mean blood pressure (BP). Alternatively, when RV afterload was increased, volume resulted in RV failure, i.e., decrease in SV (P less than 0.01) from 9.1 to 6.3 ml and a decrease (P less than 0.05) in mean BP from 97 to 65 mmHg, despite increased right ventricular end diastolic pressure (RVEDP) (P less than 0.05). Right ventricular dysfunction occurred with volume expansion, despite constant PVR and a decrease (P less than 0.01) in mean pulmonary artery pressure (PAP). In contrast to volume, norepinephrine infusion decreased biventricular filling pressures (P less than 0.01) and increased (P less than 0.01) SV from 6.2 to 11.3 ml. Accordingly, when RV afterload is increased significantly, even a relatively small increase in blood volume may result in RV dysfunction. Alternatively, inotropic agents with pressor effects may be the treatment of choice to increase CO when RV afterload is increased.