Idiopathic nephrotic syndrome (INS) of childhood is likely to be underlain by an immunopathological mechanism; we investigated the presence of immunogenetic HLA markers in this disease. Fifty-four unrelated INS-affected children, among them 20 with an allergic status, were studied for 33 HLA-A,B and 6 HLA-DR antigens. The results were compared to those obtained in 49 children with glomerulonephritis, 28 children with atopy but without nephropathy, and 91 healthy blood donors. The HLA-A and B antigen frequencies were not significantly different from normal frequencies. The incidence of HLA-DR7 was significantly increased in INS-affected patients as compared to the other groups (66.7% in patients vs 31.1% in healthy controls; corrected P value less than 0.001; relative risk = 4.4), and more so in those with atopy than in those without atopy (90% vs 46%; P = 0.002). The frequency of this antigen is not increased in atopic non-nephrotic children. No relationship between HLA-DR7, clinical outcome and steroid-responsiveness was found. We suggest that the pathogenesis of INS could be influenced by an HLA-linked immune response gene, especially in its atopy associated form.