Gamma-interferon (IFN-gamma) increases class I major histocompatibility complex (MHC) expression in human neuroblastoma cell lines. These cells are of interest because of the initial paucity of MHC expression, a paucity that is also seen in neural tumors and normal brain. The aim of this study was to define further the class I molecules, and to begin to analyze the genetic basis of the regulation. Northern blot analysis with cDNA probes for HLA and beta 2-microglobulin (beta 2-m) RNAs shows that both are present in reduced quantities (relative to a B-cell control) in control neuroblastoma cells. The levels of both RNAs are increased following IFN-gamma. This behavior parallels that of the corresponding polypeptides. Further monoclonal antibody analysis of the class I proteins from IFN-treated cells shows that both HLA-A and HLA-B are present. For two cell lines, expression of appropriate polymorphic specificities is also shown to be increased. We conclude that IFN-gamma can cause increased expression of appropriate HLA-A,B,C specificities on cells of neuronal origin. This raises the question of whether these molecules can serve predicted immunological functions.