gamma-Interferon (IFN-gamma) is known to induce expression of major histocompatibility complex (MHC) class II antigens on murine astrocytes and MHC class I antigens on murine oligodendrocytes. We studied whether the human IFN-gamma could induce the expression of Human Leukocyte Antigen (HLA)-A, B, C and -DR antigens on cultured human glia from autopsied brain white matter tissue. HLA-A, B, C antigens were induced on both human astrocytes and oligodendrocytes, whereas HLA-DR antigens were induced only on some astrocytes. From these results, it is suggested that IFN-gamma affects the expression of MHC class I and class II antigens on astrocytes and oligodendrocytes derived from human brain. The relationship between the induction of MHC class I and class II antigens by IFN-gamma and the pathogenesis of multiple sclerosis is discussed.