The frequency of various autoimmune features in 14 patients with insulin-resistant diabetes mellitus (type B) was reviewed. Twelve patients had leukopenia, high titers of antinuclear antibodies (speckled pattern), and hypoalbuminemia; 11 had elevated serum levels of IgG and high erythrocyte sedimentation rates; 7 had proteinuria and high serum levels of antibodies to DNA; and 5 had alopecia and elevated serum levels of IgA. Lupus erythematosus preparations were negative in all patients. Eight patients met the conventional criteria for the diagnosis of systemic lupus erythematosus. Three patients developed renal involvement while under care at the National Institutes of Health. Kidney tissue samples showed proliferative and membranous glomerulonephritis, tubulointerstitial nephritis, and electron-dense deposits similar to those of lupus nephritis. The lupus nephritis in these 3 patients appeared to be independent of the level of insulin-receptor antibody and glucose dysmetabolism. This study documents the presence of systemic lupus erythematosus in a large proportion of patients with insulin resistance due to autoantibodies to insulin receptors and emphasizes that careful monitoring of such patients for major complications of lupus nephritis is warranted.