Serum levels of neuron-specific enolase (NSE) were measured by radioimmunoassay at diagnosis in 122 children with widespread metastatic neuroblastoma (clinical stage IV). 96% of these patients had NSE levels more than three standard deviations above the mean for age-matched normal children. Mean serum NSE was 207 +/- SD257 ng/ml (range 10-1240 ng/ml), whereas that in normal age-matched children was 7.5 +/- 2.1 ng/ml (range 5.4-12.9 ng/ml). Analysis of survival in relation to the level of NSE at diagnosis suggested that serum levels greater than 100 ng/ml were associated with a poor outcome. This relation was highly significant in the subgroup of infants less than 1 year old at diagnosis; all 7 with serum NSE below 100 ng/ml were alive up to 36 months after diagnosis, whereas 7 of 8 with serum NSE above 100 ng/ml died within 12 months of diagnosis. Serum NSE may be a useful disease marker and a prognostic indicator in children with metastatic neuroblastoma.