The distribution of the disialoganglioside GD2 in the human nervous system was studied by immunostaining using monoclonal antibodies 3F8 and 3A7. Positive staining was detected throughout the central nervous system, predominantly in neuronal cell bodies and neuropil of the gray matter. The specific localization of reactivity in such structures as cerebellum and hippocampus differs from that of related gangliosides, suggesting that GD2 may have a distinct functional role(s) in the brain, and is not merely a metabolic intermediate. GD2 expression was also analyzed in a series of 39 neuroblastomas. Staining of both primitive neuroblastic and differentiating ganglioneuromatous elements was seen, although some tumor cell heterogeneity was noted. The results have implications for immunotherapy of neuro-blastomas using anti-GD2 antibodies.