IgA nephropathy and HSP nephritis share some similar immunological abnormalities, for example, high IgA serum concentration, existence of IgA-IC, alternative pathway activation, monocyte and B-cell activation and the same histological findings of renal biopsy. The genetic factors may play an important role in both diseases. The increased frequency of homozygous null C4 phenotypes was reported in Caucasians. But the regional variation of C4 null alleles were recognized distinctly, and the significance of C4 isotype deficiency remained unclear. We studied the relationship between IgA nephropathy and Class II and Class III HLA antigens in Japanese by not only C4 protein phenotypes but also gene analysis (TaqI, Nla IV and EcoO 109). The frequency of C4 protein isotype deficiency was the same with control groups, but significantly increased C4 gene deletion was observed in both diseases. Neither DR4 nor DQB4/8/9 related to C4 gene deletion, but the total C4 serum concentration was lower in gene deletion groups. We could not detect any deviation between C4A and C4B locus deletion by Nla IV and EcoO 109 analysis. Considering the changing process of C4A to C4B, there is a possibility that the mechanism of deletion process itself causes the elevated sensitivity to the diseases.