The relationship between serum creatine kinase brain-specific isoenzyme (CK-BB) activity immediately after birth and neurodevelopmental outcome at two and four years corrected age was studied prospectively in 45 preterm infants (less than 34 weeks gestation). Nine infants died during the neonatal period and one was lost to follow-up. Of the 35 children available for follow-up, seven had motor disabilities: four severe diplegia, two mild to moderate diplegia and one hemiplegia. No relationship existed between these motor disabilities and serum CK-BB activity after birth. There seemed to be a relationship between increased serum CK-BB after birth and low scores on the Bayley Scales of Mental Development, but this did not reach statistical significance. At the age of four years, four of the five survivors with high serum CK-BB activity after birth (greater than 25U/L) needed special schooling because of mental retardation. Increased serum CK-BB activity after birth may be associated with delayed mental development, but further study is needed, especially of asphyxiated infants.