Brain-type isoenzyme of creatine kinase was measured serially in 45 healthy and 22 severely asphyxiated term infants. The enzyme was measured in cord blood and in venous, capillary, or arterial blood at six to eight hours, 24 to 30 hours, and 72 to 80 hours after birth. In the healthy infants a brief rise of CK-BB occurred at six to eight hours; CK-BB activities were greater than 2.5 log-transformed standard deviations above the mean of the control values in ten of the asphyxiated infants and in none of the control infants. When normal CK-BB activity was used as a predictor of good neurologic outcome and elevated CK-BB as a predictor of subsequent neurologic abnormality, the outcome was predictable from the CK-BB activity in 17 of 22 cases (77%) and in 11 of the 12 survivors (92%). Eight of the 12 surviving infants had neonatal seizures and outcome was predictable from CK-BB activity in all cases. We conclude that serum CK-BB activity, especially when measured in cord blood and at six to 12 hours of life, correlates with neurologic outcome after severe asphyxia, and that measurement of CK-BB compares favorably with radionuclide and computerized tomographic scanning as a method of predicting neurologic outcome after asphyxia.