Expression of the defined subtypes of HLA-class II antigens DQ, DR, DP, as well as of a putatively new HLA-class II determinant DY was evaluated with specific monoclonal antibodies on frozen sections of 15 normal kidneys, as well as of renal tissue of 65 patients with different forms of glomerulonephritis (GN). In normal kidney HLA-DR and/or -DY versus DQ or DP antigens were shown to be differentially expressed on subpopulations of glomerular and interstitial cells, as well as vascular endothelia. Normal proximal tubular epithelia lacked HLA-DQ and -DP antigens, but carried -DY and variably -DR products constitutively. In comparison, aberrant presence of HLA-DQ and/or -DP antigens was found on proximal tubular cells in the majority of patients with rapidly progressive (RPGN), membranoproliferative GN (MPGN), or focal glomerular sclerosis (FGS), but more rarely observed in other forms of proliferative or non-proliferative GN. In addition all cases with RPGN revealed reduction of HLA-DQ, -DR, -DP or -DY+ glomerular cells. Decline of HLA-DP and/or -DR+ glomerular cells was variably seen in mesangioproliferative glomerulonephritis (MesPGN) and MPGN, whereas in FGS HLA-DQ antigens appeared to be increased in glomeruli. HLA-DQ, -DR, -DY+ interstitial cellular infiltrates were present in RPGN, FGS and MPGN and only occasionally occurred in other forms of GN. Altered renal expression of HLA-class II antigens may indicate specific sites of immunologically-mediated kidney injuries in GN.