A 4-MDa component, recovered from uterine luminal secretions of gilts on d 15 of pregnancy, was assessed for suppression of the lytic responses from natural killer (NK) and lymphokine-activated killer (LAK) effector cells. Each cell type originated from preparations of peripheral blood lymphocytes (PBL), and the LAK cells were generated from the incubation of PBL with interleukin-2. The PBL and LAK cells were cultured for 5 d with and without the 4-MDa component. Following culture, the cells were incubated (22 h) with NK-sensitive K-562 target cells at varying effector:target cell ratios (25:1 to 200:1). Lytic activity was assessed with the chromium-51 release assay. Additional experiments were conducted in order to determine whether suppressor activity of the 4-MDa component was time-dependent and associated with transforming growth factor-beta2 (TGF-beta2). For effector:target cell ratios combined, the 4-MDa component suppressed the lytic activity of PBL but failed to affect the LAK cells. Suppression of NK-mediated lysis occurred by d 3 of the 5-d culture period. In addition, suppressor activity of the 4-MDa component was reversed by a neutralization antibody to TGF-beta2. In conclusion, the 4-MDa component with TGF-beta2 activity suppressed the lytic responses of porcine NK cells.