HLA-A, B and DR typing was performed on a total of 236 patients with chronic glomerulonephritis (CGN) which were diagnosed by renal biopsies evaluated by light microscopy, direct immunofluorescent staining and whenever indicated electron microscopy. The interrelationship between the HLA system and the histopathologic classification of CGN was examined. There were 20 patients with benign recurrent hematuria (BRH), 82 with IgA nephropathy (IgA-N), 24 with proliferative glomerulonephritis (PGN), 47 with minimal change nephrotic syndrome (MCNS), 4 with membranous nephropathy (MN), 43 with membranoproliferative glomerulonephritis (MPGN) and 16 with focal glomerulosclerosis (FGS). The following results were obtained: 1) Antigens from different loci were associated with different subgroups of CGN. There were three types of associations; a) HLA-A locus associated as found in PGN, b) HLA-B locus associated as found in BRH and c) HLA-DR locus associated as found in MCNS. IgA-N, MPGN and FGS seemed to be included in this group. 2) The association of HLA-A locus antigens with MCNS could be subdivided by age o onset suggesting that in MCNS HLA-A antigens are linked to disease expression. 3) A heterogeneity in IgA-N is suggested by its association with different HLA antigens; a) a HLA-B37 associated group, b) a HLA-DR4 or DYT associated group and c) a HLA-DEn (Dw 6.1) or B12 associated group. These data suggest differences in the mechanisms of HLA and disease association in each histopathologic subtype of CGN.