Neuroblastoma, one of the most frequent solid tumors found in childhood, is very rare in Down's syndrome subjects. This lack could possibly be due to overproduction of S-100 b protein for the following reasons: 1) the gene coding for S-100 b protein is situated on chromosome 21, and the protein is overproduced via a gene dosage effect; 2) S-100 b protein is found in glial cells and Schwann cells of the central and peripheral nervous system and has been shown to have a differentiating effect on normal neural cells; 3) neuroblastomas with a stroma rich in S-100 protein have a good prognosis. Preliminary studies demonstrated an inhibition of growth of two human neuroblastoma cell lines in the presence of S-100 b protein compared to controls. It is postulated that S-100 b protein may inhibit the development of neuroblastomas in Down's syndrome either antenatally, or after birth and may be a therapeutic agent against neuroblastoma.