The HLA systems of forty Japanese patients with adult-onset nephrotic syndrome and biopsy-proven minimal change were investigated. HLA-DRw8 was found in 35% of the patients and HLA-DQw3 in 95%, compared to 12.6 and 63.1% of the control, respectively (DRw8: and Pc less than 0.01, RR = 3.74; DQw3: Pc less than 0.02, RR = 11.1). The phenotype frequencies of all but one HLA-DR antigens, DR4, DR5, DRw8, and DRw9 associating with DQw3, were observed to increase (patient vs. control: DR4, 65 vs. 41.4%; DR5, 10 vs. 4.3%; DRw9, 20 vs. 23%). These results suggest that HLA-DQw3 may be a primary genetic marker associated with a major susceptibility gene to adult-onset minimal change nephrotic syndrome in the Japanese population.