Bru-Pel and Brucella abortus lipopolysaccharide (LPS) were tested for both macrophage activation and antitumor activity in an artificial metastasis model. Resting macrophages were rendered nonspecifically tumoricidal for MBL-2 lymphoblastic leukemia target cells by exposure to Bru-Pel at greater than or equal to 1 ng/ml of culture medium. B. abortus LPS failed to activate macrophages in vitro at all concentrations tested. Ip treatment of homozygous nude mice with Bru-Pel induced cytotoxic macrophages, indicating that Bru-Pel activated macrophages through a thymic-independent process. An artificial metastasis model was developed where single-cell suspensions of Madison 109 lung carcinoma were inoculated iv into syngeneic BALB/c mice. Bru-Pel, but not B. abortus LPS, strikingly inhibited tumor-colony formation in the lungs. Although Bru-Pel contains endotoxin, the data demonstrate that endotoxin is apparently not the active component by which Bru-Pel activates macrophages and enhances host resistance to cancer.