HLA and Gm phenotypes were compared in 53 patients with unequivocal systemic lupus erythematosus (SLE) and in 180 healthy subjects. SLE was associated with HLA‐B8 (relative risk (RR) = 3.5,P<0.001) and with HLA‐DR3 (RR = 2.8,P13) and, in contrast, the risk was decreased in subjects with HLA‐B40 (RR = 0.3). The risk of SLE in subjects who were heterozygous for the Gm phenotypes a,f,x; b,g was increased (RR = 2.0,P= 0.03) relative to the risk in subjects who were homozygous for these Gm phenotypes. These findings suggest that susceptibility to SLE is influenced by one or more genes in linkage disequilibrium with the HLA‐B8‐DR3 haplotype, by “augmentor” or “protector” genes associated with other HLA antigens and by separate genes, possibly VHgenes, in linkage disequilibrium with the