Non-neoplastic mammary gland, 20 benign tumors and 206 carcinomas of the breast were immunohistochemically examined for expression of HLA-A, -B, -C, HLA-DR, -DP, and -DQ molecules and the HLA-D associated invariant chain (Ii). In contrast to cells from benign lesions, tumor cells of 51.2% of carcinomas had an abnormally low content of HLA-A, -B, and -C determinants ranging from reduction of antigenic density per cell (28.8%) over an incomplete (15.6%) to complete loss of antigens (6.8%). Associated with lymphohistiocytic stromal infiltrates, HLA-D/Ii determinants were found to be induced in benign duct and acinar epithelium after the order Ii greater than or equal to HLA-DR greater than or equal to HLA-DP greater than or equal to HLA-DQ. These antigens were also expressed, mostly noncoordinately, in 55.5% of carcinomas, and in 98 cases according to the above order. In 28.6%, Ii expression clearly exceeded HLA-D antigen expression; conversely, 6.2% contained HLA-DR+/Ii- tumor cell subsets. In breast carcinoma, the association of reduced HLA-A, -B, and -C expression and a noninduction of HLA-DR was highly significant (P less than 0.0009), suggesting an abnormal signal acting down-regulating on the expression of both classes of antigens. Because the modality of HLA-A, -B, and -C and HLA-D/Ii expression correlated with neither tumor type nor grade, it might be an independent parameter.