CBA/CaH-kdkd mice develop a spontaneous and chronic tubulointerstitial renal disease which is characterised by mononuclear cell infiltration, tubular collapse and cystic dilatation of tubules. The pathogenic mechanisms of renal injury have not been fully elucidated in this model. We have analysed the nature of infiltrating cells and the expression of MHC class II antigens, cytokines and adhesion molecules in CBA/CaH-kdkd kidneys at various disease stages. Using immunohistochemical techniques we found that kdkd kidneys are characterised by abundant macrophage and dendritic cell infiltration with fewer T cells with CD4+ and CD8+ phenotypes. Interestingly, MHC class II antigens were not induced on renal tubules. The proinflammatory cytokine, TNF-alpha, was markedly enhanced in kdkd kidney (up to fourfold), whereas the T cell-specific cytokine, IFN-gamma, increased less (less than twofold). ICAM-1 and VCAM-1 were markedly overexpressed by injured proximal tubules. ICAM-2 and PECAM-1 were constitutively expressed on glomerular capillaries and vascular endothelium in normal kidneys and did not change in CBA/CaH-kdkd mice. In conclusion, tubulointerstitial nephritis in CBA/CaH-kdkd mice is characterised by prominent macrophage infiltration and abundant expression of ICAM-1 and VCAM-1 on injured renal tubules. The lack of MHC class II antigens on injured tubules suggests that the kd gene defect could generate a secondary renal inflammatory response which is characterised by prominent macrophage infiltration and a relative scarcity of T cells.