A murine monoclonal antibody, MoAb B1B6 (IgG1 chi), which recognizes the large sialoglycoprotein (LSGP) on human peripheral blood lymphocytes (PBL) effectively enhanced the spontaneous cytotoxicity of these cells against the natural killer (NK)-sensitive target cells K562 and Molt-4. Whereas preincubation of the lymphocytes with MoAb B1B6 resulted in increased cytotoxicity, preincubation of the target cells had no effect, indicating that the MoAb amplified cytotoxicity at the effector cell level. Kinetic analysis of the data revealed no differences between the control and the MoAb-treated lymphocytes with regard to Vmax, usually considered to reflect the overall lytic potential of the cells. The slopes of the saturation curves, however, differed significantly for the two cell populations, indicating a substantial increment in the activity of the MoAb-treated cells. When studied at the single cell level and with K562 as targets, treatment of PBL with the MoAb resulted in the recruitment of new effector lymphocytes from the pool of non-binding cells. In contrast, when Molt-4 cells were employed as targets, no additional effector cells were recruited. These results indicate that the enhanced cytotoxicity induced by MoAb B1B6 is the result of either recruitment of new effector lymphocytes or of an increased recycling capacity of preexisting effector cells. Together with previous observations, these findings support the conclusion that LSGP belongs to the set of surface molecules which regulate human lymphocyte activation.