Twelve of 44 black American patients with systemic lupus erythematosus (SLE) (27%) studied during periods of disease activity had increased levels of IgG antibodies against cardiolipin (IgG aCL). IgG aCL occurred almost exclusively in patients who had a partial genetic deficiency of C4A or C4B. Eleven of 29 patients (38%) with a C4A or C4B deficiency allele had IgG aCL, compared with 1/15 patients (7%) who did not have C4A or C4B deficiency allele (p = 0.04). During periods when SLE was less active clinically, IgG aCL levels returned to normal in 10/12 patients. Active SLE, rather than null alleles, appeared to be associated with low C4 levels in patients with IgG aCL.