Major histocompatibility complex (MHC) antigens play important roles in immune responses. MHC class II molecules serve as restriction elements for cells presenting antigens to CD4-positive helper T-cells. They also function as histocompatibility antigens responsible for graft rejections by stimulating allogenic reaction. Furthermore, it was reported that the expression of class II antigen on tumor cells increases immunogenicity in mice by a mechanism involving class II molecule positive tumor cells which present tumor associated antigens to host immune cells or induce allogenic reactions against tumor cells. Class II molecules associate with the HLA class II antigen-associated invariant chain (Ii) as soon as class II molecules are produced in the rough endoplasmic reticulum. Ii is considered to block the binding of endogenous peptides to class II molecules, and to be a signal for transporting class II molecules to endosomes. Both functions of Ii are essential for the function of class II molecules. To investigate the association between renal cell cancer (RCC) and the host's immune system, we immunohistochemically examined 60 RCCs for the expression of Ii, class II and class I antigens on RCC and the degree of lymphocytic infiltration. We detected Ii to varying degrees on 53 out of 60 RCC tissues but none on normal renal tubular cells. Compared with class II antigens, they were detected in the order DR > or = Ii > or = DP not equal to DQ. A significant correlation was found between the expression of Ii and the degree of lymphocytic infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)