The effect of culture supernatant of MT-2 cells on human immunodeficiency virus (HIV)-producing cells, MOLT-4/HIVHTLV-IIIB cells, was examined. As compared to the effect on MOLT-4 cells, parent cells not infected with HIV, a selective cytotoxic/cytostatic effect on MOLT-4/HIVHTLV-IIIB cells was observed 4 days after treatment with up to 640-fold-diluted MT-2 supernatant. Furthermore, under similar conditions, a 2- to 6-fold increase in the number of HIV particles was detected in the culture of MOLT-4/HIVHTLV-IIIB cells 6 hr after treatment. Complete blocking of these effects by anti-lymphotoxin monoclonal antibody, but not by anti-tumor necrosis factor antibody, indicates that these effects of MT-2 supernatant on MOLT-4/HIVHTLV-IIIB cells are attributable to a lymphotoxin-related cytotoxic factor.