Renal biopsies (n = 45) from patients with various forms of glomerulonephritis (GN), comprising mesangial IgA-GN (n = 25), focal glomerular sclerosis (n = 13) and acute GN (n = 7), were examined by double staining immunocytochemistry (APAAP, streptavidin-peroxidase) using unconjugated monoclonal antibodies (Ab) against--(i) the CD1b antigen expressed on dendritic cells (DCs), (ii) the invariant chain (Ii), and (iii) biotin-conjugated Ab against HLA-DR. In normal control kidneys (n = 7) without interstitial inflammation, CD1b-positive DCs were not detected. Glomerular endothelial cells and a few cells in mesangial areas showed double staining with the Ab against HLA-DR in Ii. In GN without active interstitial inflammation (n = 9), CD1b-positive DCs were not found. In biopsies with interstitial inflammation (n = 36) CD1b-positive DCs were found interspersed among other inflammatory cells. In seven of the biopsies showing IgA-GN DCs were seen in the vicinity of those glomeruli that exhibited either crescents or glomerular sclerosis with splitting of Bowman's capsule. In proximal tubular epithelial cells de novo expression of HLA-DR/Ii-chain was only seen when DCs were present. We conclude that in different forms of GN: (i) CD1b-positive DCs play an important role in the development of interstitial inflammation, and (ii) their presence may be related to the de novo coexpression of HLA-DR/Ii in tubular epithelial cells, possibly mediated through the production of interferon gamma and other cytokines.