Class II major histocompatibility complex (MHC) products are important molecules on various antigen-presenting cells and induce a T cell-specific immune response. The distribution of class II MHC molecules in the normal canine kidneys of dogs with tubulointerstitial nephritis was investigated by using a sensitive immunocytochemical method. In the normal canine kidney, class II MHC molecules were detected in interstitial 'dendritic' cells. In cases of tubulointerstitial nephritis, however, the expression of class II MHC molecules extended to other renal elements such as the epithelial cells of cortical and medullary tubules and, in some cases, the endothelial cells of peritubular capillaries. The tubular expression of class II MHC molecules was enhanced in dogs with higher levels of proteinuria. The results suggest that heavy proteinuria may be one triggering factor in canine tubulointerstitial damage, probably mediated by the reabsorption of filtered cytokines and immunogenic peptides which induce tubular epithelial cells to behave as immune accessory cells.