The role of polymorphonuclear leukocytes (PMNs) as effector cells in tumor lysis was investigated in vitro. PMNs were obtained from the peritoneal cavity of C3H/He Mice injected ip with 2 ml of 12% casein sodium. These PMNs could lyse murine MM46 tumor cells in the presence of the plant lectin, wheat germ agglutinin (lectin-dependent PMN-mediated cytolysis). PMNs alone did not cause cytolysis. PMNs obtained 6 hr after casein injection were effective against tumor target cells but those obtained 3 hr after the injection were not. Other lectins, such as concanavalin A, phytohemagglutinin, pokeweed mitogen, soybean agglutinin, Ulex europaeus agglutinin, Lens culinaris hemagglutinin and Bauhinia purpurea agglutinin, did not cooperate with PMNs in tumor lysis. Antitumor antibody was another mediator that induced tumor lysis in cooperation with PMNs (antibody-dependent PMN-mediated cytolysis). These results indicate that PMNs can lyse tumor cells in the presence of appropriate mediators.