The expression of HLA-DR, HLA-DP and HLA-DQ antigens was studied in an unselected series of 66 B-cell lymphomas by means of immunohistology using monoclonal antibodies against non-polymorphic determinants in a sensitive immunoperoxidase technique. In addition, the expression of the MHC class-II antigen-associated invariant chain (li) was examined. The tumors were classified according to the Kiel classification, 30 being of high-grade and 36 being of low-grade malignancy. Only 6 lymphomas of high-grade and 16 lymphomas of low-grade malignancy showed coordinate strong expression of all HLA class-II antigens and invariant chain as observed in the normal peripheral B cell. Six further tumors of high-grade and 8 tumors of low-grade malignancy contained tumor-cell subsets with reduced expression of one or several of the antigens. Eighteen lymphomas of high-grade and 12 lymphomas of low-grade malignancy contained varying tumor-cell subsets that were negative for HLA-DR, -DP, -DQ and li in a selective or combined manner. Three highly malignant tumors were devoid of all class-II antigens and li; 2 highly malignant tumors expressed invariant chain only. The presence of high-grade malignancy was significantly correlated with the occurrence of tumor cells lacking HLA-DR (p = 0.004), HLA-DP (p = 0.013), HLA-DQ (p = 0.007) or li (p = 0.024).