We have studied the effect on the interleukin (IL-) 2-dependent human T cell growth of two distinct monoclonal antibodies (Mab), D1-12 and 4F2, with specificity for common determinant of human Ia antigens and for a differentiation antigen expressed on all activated T cells, respectively. Strong inhibition of cell growth was found in cultures supplemented with the anti-Ia D1-12 Mab but not in cultures supplemented with 4F2 Mab. These results were obtained when either total mixed leukocyte culture (MLC) T cells or an MLC-derived T cell clone were used as indicator cell systems for IL-2 activity. The inhibition of cell growth appears to be mediated by a direct interaction of D1-12 Mab with the cells and not by a direct inactivation of the growth factor, as addition of the antibody to murine MLC T cells, which do not express the determinant defined by D1-12 Mab, resulted in no inhibition of their proliferation induced by the same source of human IL-2.