The mechanism of development of hydrops fetalis in severe isoimmunization has been subject to speculation. We performed pulsed Doppler assessment of cardiac output in 13 severely isoimmunized fetuses before and after intravascular transfusion and compared the results with 37 control fetuses between 20 and 34 weeks' gestation. The cardiac index of the anemic fetuses was significantly greater than that of the control group. A significant (right ventricle, p less than 0.01; left ventricle, p less than 0.02) increase in indexed output was noted from both ventricles and in the combined ventricular output (mean +/- SEM 644 +/- 35.3 ml/kg/min in control fetuses versus 879 +/- 86.0 ml/kg/min in anemic fetuses, p less than 0.006). An increase in cardiac output was also noted when anemic fetuses were compared with gestational age-specific norms. We conclude that severely anemic fetuses of isoimmunized pregnancies tend to have significantly higher cardiac output than do unaffected fetuses and that this high output state may play a part in the development of hydrops fetalis.