The relation between IgA hyperproduction and restriction fragment length polymorphism (RFLP) of the immunoglobulin heavy chain switch (S) region was examined in Japanese patients with IgA nephropathy (IgAN) using Southern blot hybridization. Polymorphism in the S regions of IgM, IgA1 and IgA2 (SA2) was detected. A significant increase in the frequency of heterozygous phenotype of SA2 was shown in the patients. These patients showed a significant increase in the amount of serum IgA, IgA bearing cells and levels of proteinuria. Although two reports on RFLP of the S region have been published in Europe, the results differed. A comparison of the three reports showed different frequencies in the phenotype of the S region between Caucasian and Japanese patients. These results suggested that there is heterogeneity at the S region in IgAN patients in various countries and that this polymorphism might be associated with IgA hyperproduction and the development of proteinuria in Japanese patients.