Gas chromatographic carbohydrate analyses of IgG from 30 patients with idiopathic systemic lupus erythematosus (SLE) revealed lower content of galactose when compared to that in 36 controls of similar ages (mean +/- SD, 3.18 +/- 0.66 vs 3.82 +/- 0.41 galactose residues/mole of IgG, P < 0.001). Abnormal galactosylation was observed in 60% of SLE patients. Analyses of IgG from 58 members of five families, characterized by a high frequency of SLE and other autoimmune diseases and serological abnormalities, and 51 controls of similar age range revealed that IgG galactose deficiency was detectable not only in some members with clinical and serological abnormalities (P < or = 0.001), but also in those without evidence of autoimmune diseases or abnormal serologies (P < or = 0.001). These data indicate that abnormal galactosylation of IgG frequently occurs in asymptomatic members of families with a high frequency of SLE and other autoimmune diseases and suggests that this abnormality may be an indicator for the development of these diseases.