Cardiovascular adjustments during liquid ventilation were investigated in seven cats. Cardiac output (CO) and regional blood flow were measured with radioactive microspheres during both spontaneous air breathing (control) and ventilation with fluorocarbon liquid, FC-80. CO was found to decrease 48% (P less than 0.05) during liquid breathing as compared to control. This decrease largely reflected a reduced stroke volume. Despite the decreased CO, mean arterial pressure remained unchanged, indicating a 48% increase (P less than 0.002) in total peripheral resistance (TPR). Secondary to the reduced CO and increased TPR, extensive redistribution of blood flow occurred during liquid ventilation. The arterial lactate concentration and lactate-to-pyruvate ratio (L/P) were significantly increased (P less than 0.02). Furthermore, the increase in L/P correlated with the decrease in CO (r = 0.70; P less than 0.01). In turn, the significant decrease in pH during liquid breathing was found to correlate with the increase in L/P (r = 0.85; P less than 0.001). These data clearly demonstrate signficant alterations in cardiovascular dynamics during liquid ventilation with secondary hyperlactatemia and acidosis.