We have analysed class II molecules (HLA-DR) expression in human fetal nerves at different stages of gestation, in human control nerves and in nerves of patients with peripheral neuropathies of different aetiology. Immunochemical demonstration of HLA-DR antigens was also performed on isolated human Schwann cells at different times in culture, from the same nerves. In normal nerves, HLA-DR positive material is localized only on endothelial and perivascular cells and in rare perineurial and endoneurial cells. In fetal nerves, HLA-DR positive material is already present by the sixteenth week of gestation. Quantitative analysis of HLA-DR molecules density in pathological nerves showed a wide heterogeneity in different neuropathies with no correlation between the type of pathology and the intensity and pattern of staining. Cultured human Schwann cells obtained from fetal, normal adult and pathological (vasculitic neuropathy) nerves were HLA-DR positive and the percentage of positive cells increased with time in culture. DR antigen appearance on human Schwann cells may reflect not only an immunologically-mediated phenomenon but also a dependence on axon-Schwann cell interaction.