We studied the immunoglobulin Gm allotypes in 41 patients with glomerular nephritis caused by autoantibodies to glomerular basement membrane (GBM). Gm phenotypes of all 41 patients were attributable to combinations of the 3 Gm haplotypes commonly found in Caucasoid populations; identified by the allotypes Gm 1,21 (ag), Gm 1,2,21 (axg), and Gm 3,5,11 (fb). The incidence of the putative haplotype Gm 1,2,21 (axg) was greatly increased in the patients being present in 22 of 41 (56%) of patients compared to 28 of 167 controls. (Pcor = 1.5 X 10(-5]. The increase in Gm 1,2,21 (axg) was attributable entirely to presumed heterozygotes with the phenotype Gm 1,2,21;3,5,11 (axg;fb), with concomitant decreases in the frequencies of patients with the phenotypes Gm 1,21 (ax) and with Gm 3,5,11 (fb). Heterozygotes at Gm loci had higher titers of anti-GBM antibodies irrespective of the presence of Gm 1,2,21 (axg). Thus genes within or closely linked to the Gm complex in addition to HLA linked genes influence susceptibility to or clinical expression of anti-GBM disease.