The expression of major histocompatibility complex (MHC) class I and II molecules is important in autoimmune disease processes. Experiments to determine this expression in peripheral nervous tissue cells were carried out utilizing Schwann cells in association with neurons and fibroblasts cultured from explants of human fetal dorsal root ganglia (DRG) at 6 and 15 days in vitro (DIV). Previous studies have examined the expression of these molecules only on isolated Schwann cells. The expression of MHC molecules was determined using immunohistochemistry. When the cultures were incubated with recombinant human interferon-γ (IFN-γ), only the Schwann cells expressed class II MHC molecules. This expression increased with time to a maximum by 15 DIV, a stage by which some Schwann cells had ensheathed axonal bundles and others had ensheathed individual axonal lengths. No class II MHC molecules were seen in cultures without IFN-γ. MHC class I molecules were present on Schwann cells and also on fibroblasts at low levels without IFN-γ but the level of expression was much increased after IFN-γ incubation. Maximum expression of class I MHC molecules occurred by 24 h.