Neoplastic cells from patients with a variety of B- or non-B/non-T-lymphoid malignancies, including chronic lymphocytic leukemia, various histologic types of non-Hodgkin lymphoma and acute lymphocytic leukemia, showed strong variation with respect to stimulatory capacity in mixed lymphocyte culture (MLC). MLC stimulatory capacity was either normal or strongly decreased in comparison with that of normal lymphocytes despite the expression of HLA-DR antigens and p23,30 ("Ia-like") determinants on the tumor cells of all patients. Strongly decreased stimulatory capacity of HLA-DR-positive tumor cells could not be ascribed to suppressive activity of the tumor cells. Tumor cells from three patients with a T-cell malignancy failed to stimulate in MLC and did not react with anti-p23,30 serum. The decreased stimulatory capacity of many DR-positive neoplastic cells is ascribed either to altered membrane presentation of DR antigens or to the absence of MLC stimulatory determinants specified by genes closely linked to, but different from, those coding for DR.