Although the etiology and pathogenesis of IgA nephropathy is not fully understood, it has been classified as an immune-complex induced glomerulonephritis caused by an immunological mechanism. Forty-two patients with primary IgA nephropathy underwent tissue typing for HLA-A, B, and DR antigens by the standard method using a microlymphocytotoxicity test. There was no significant correlation between HLA-A and B antigens and this disease. However, the frequency of HLA-DR4 was 57.1% in the patients with normal renal function, 85.7% in those with decreased renal function, 100% in dialysis patients, and 39.2% in the control group. It is statistically significant in the patients with renal dysfunction (corrected P less than 0.05). Our results suggest that the HLA system may play an important role in the occurrence and exacerbation of IgA nephropathy in the Japanese population.