The expression of the HLA-DR antigen, a Class II HLA antigen, was analyzed in 41 cases of gastric carcinoma (23 intestinal-type and 18 diffuse-type according to a modified Lauren classification) using a monoclonal antibody that is reactive to this antigen in routinely formalin-fixed, paraffin-embedded tissue sections. Seventeen cases of intestinal-type gastric carcinoma and two cases of diffuse-type gastric carcinoma were positive for the HLA-DR antigen. The staining in intestinal-type carcinoma generally was stronger and more extensive than in diffuse-type carcinoma, which showed only weak and focal staining. The difference in the frequency and pattern of staining between intestinal and diffuse-type gastric carcinoma supports the concept that these are two distinct subtypes of gastric carcinoma.