Previous work showed that each of four human neuronal cell lines expresses less than or equal to 0.5% of the HLA-A,B,C and beta 2-microglobulin seen in glial, lymphoid, and other cell types, and there is a corresponding weak expression in neuroblastoma tumor and adult brain. Here, we probe the genetic basis of this weak expression. For each of three neuroblastoma cell lines, we show that HLA-A,B,C and beta 2-microglobulin can be induced by interferon and that the induction occurs within every cell of the population. Class II (Ia) molecules are not detected. Microscopic assay and radioimmunoassay of intact cells suggest that the induced antigen appears at the cell surface as well as within each cell. Immunoblot analysis confirms that the induced proteins have the structure of class I molecules. Thus, the normal weak HLA and beta 2-microglobulin expression of these cell lines appears to reflect a regulatory control rather than a primary genetic lesion. According to current theory, lack of HLA-A,B,C should protect transformed, infected, or damaged neurons--but also neurons in neural transplants--from T-cell-mediated immunosurveillance. The possibility that neuronal HLA-A,B,C expression may be under regulatory control is of importance in this context.