Non-neoplastic mammary glands and 203 carcinomas of the breast were examined immunohistochemically for expression of HLA-DR, -DP, and -DQ molecules and the HLA-D-associated invariant chain (Ii). According to the reaction of normal breast epithelium in the course of chronic inflammation, these antigens were found to be induced in 120 carcinomas. In 106 of these the order was Ii greater than or equal to HLA-DR greater than or equal to HLA-DP greater than or equal to HLA-DQ. The extent of induction of these sequentially expressed antigens correlated with the density of local lymphohistiocytic infiltration (Ii: p = 0.003; HLA-DR: p = 0.0005; HLA-DP: p = 0.0000005; HLA-DQ: p = 0.01). Therefore, Ii/HLA-D antigen expression of carcinoma cells in local association with inflammation was regarded as an adequate reaction. The presence of these antigens in the absence of inflammation was regarded as "inadequate hyper-expression", and was found in 14 cases involving Ii, in 8 involving HLA-DR, and in 1 case each involving -DP and -DQ molecules. In contrast, 20 cases expressed minimal/no Ii despite heavy inflammatory infiltration. This "inadequate hypo-expression" was also found in 25 cases involving HLA-DR, in 30 involving -DP and in 40 involving -DQ determinants. Combining the 2 variants showed that at least 54 cases (26.6%) were characterized as being dysregulated. "Adequate vs. inadequate Ii/HLA-D antigen expression" did not correlate with tumor grading and might therefore be an independent parameter.