OBJECTIVE To investigate the relationship of creatine phosphokinase and its isoenzymes with fetal asphyxia and risk at birth. METHODS Thirty-five pregnant women with high-risk pregnancy were studied. RESULTS In 21 patients, fetal distress was diagnosed by interpretation of the fetal heart rate tracing (FHR). The remaining 14 women, having normal fetal cardiotocography, were considered as the control group. Total CK and its isoenzymes activity was measured in cord sera and 24 h after birth in peripheral blood. Abnormal FHR patterns correlate well with elevated enzyme activities. Total CK and its isoenzymes (CK-MM, CK-MB, and CK-BB) exhibited higher values in asphyxiated infants as compared to normal neonates. Electrocardiographic ischemia occurred in seven newborns who had elevated CK-MB and CK-BB levels, both at birth and within 24 h postpartum. Chromatographic study showed in normal neonates that the predominant isoenzyme was CK-MM, whereas CK-BB activity was negligible. In the newborns with abnormal FHR, CK-MB and CK-BB were increased with predominance of CK-MB. CONCLUSIONS Antepartum fetal distress is associated with release of CK-BB, and particularly CK-MB; therefore, these biochemical markers may indicate either brain or myocardial damage.