Autoimmune mice carrying the lprcg/lprcg(lprcg),lpr/lpr(lpr),gld/gld(gld) and Yaa genes exhibit massive lymphoproliferation and a systemic lupus erythematosus-like syndrome. The surface markers of abnormally expanded lymphocytes used were Thy-1+, CD4-CD8- (double negative, DN) and CD45+ for lprcg, lpr, gld and (lprcg X gld) hybrid (F1-lprcg-gld) mice, and Ig+ for Yaa mice. To characterize the cell surface properties and differentiation pathway of lymphocytes in autoimmune mice, the cell electrophoretic mobility (EPM) was determined for the lymph node (LN), spleen and thymus cells. The EPM of lymphocytes derived from swollen LN was of the T cell type in lprcg, lpr, gld and F1-lprcg-gld mice, but of the B cell type in Yaa mice, indicating that the EPM of abnormally proliferated lymphocytes in autoimmune mice reflects their origin, and that the surface properties detected as a net negative charge were the same in abnormal and normal lymphocytes. The electrophoretic behavior of whole thymocytes was also the same in autoimmune and normal mice. The DN, and CD4+CD8- and CD4-CD8+ (single positive, SP) thymocytes from normal mice exhibited high EPM, while CD4+CD8+ (double positive, DP) thymocytes exhibited low EPM. According to the recent concept of intrathymic T cell differentiation (Schwartz, R. H., Cell. 1989, 57, 1073-1081), it is suggested that EPM of thymocytes may change with maturation in the following manner: DN thymocytes with high EPM----DP thymocytes with low EPM----SP thymocytes and autoimmune DN T cells with high EPM.