The inhibitory effect of cells from leukemic spleens on the immune functions of normal lymphocytes was studied. Suppressor cells were obtained as the nonadherent fraction (NA) from splenic tumors of mice infected with MuLV-Moloney. This fraction (NA MuLV- M) contained less than 10% membrane Ig-positive (Ig+) cells, 45 to 60% theta-positive cells (theta+) and 40 to 50% naught cells (theta-, Ig-). Similarly prepared fractions from normal control spleens (NAc) containing 75 to 90% theta+cells and less than 10% Ig+ and naught cells were utilized in control cultures. Addition of the NA MuLV- M cells into cultures (Marbrook system) of normal spleen cells with sheep red blood cells suppressed the specific antibody response determined by the number of hemolytic plaque forming cells (PFC). The PFC response was significantly suppressed at a suppressor cell to responder cell ratio of 1:100, and was completely abolished at a ratio of 1:10 or higher. The control NAc fraction showed some inhibitory effect only at high suppressor to responder ratios (1:2 or 1:1). In contrast, the suppressive effect of NAMuLV-M on mitogen-induced 3H-thymidine incorporation in normal B and T cells was much weaker. Very little, if any, suppression occurred at the ratio of 1:100 or 1:10, however, about 50% decrease in DNA synthesis was observed at the ratio 1:2 or 1:1. On the basis of this differential suppressive effect, it is suggested that leukemic spleen cells can suppress the function of immunocompetent cells by more than one mechanism.