Creatine kinase brain isoenzyme (CK-BB) was determined in cerebrospinal fluid of 150 neonates by a newly developed immunoenzymatic assay. Newborns with a documented neurologic disorder (intraventricular hemorrhage, postasphyxial encephalopathy, central nervous system infection, or persistent periventricular intraparenchymal echodensities) showed markedly higher concentrations of immunoreactive CK-BB than did the normal newborns or those with subarachnoid hemorrhage. In neonates with seizures the data suggest that the underlying neurologic disorder accounts for the higher CK-BB values and not the seizures per se. High concentrations of CK-BB in the neonatal period were followed by poor short-term outcome.