Summary: The immunomodulatory and anti-tumor activity of Bru-Pel, an aqueous-ether extracted residue of Brucella abortus (strain 456), was investigated. Bru-Pel was administered to C57BL/6 mice intraperitoneally (i.p.) and tested for its effect on natural killer (NK) cell activity in spleen cells, liver, and peritoneal cavity. Three days after injecting 100 m-g of Bru-Pel i.p., the cytotoxicity of spleen cells against YAC-1 target cells, assessed by LU20 increased by —two-fold and nonparenchymal cells of liver by <six-fold. The highest stimulatory effect of Bru-Pel was seen with peritoneal exudate cells, and 47- fold augmentation of NK cell activity was observed. Bru-Pel treatment made spleen, liver, and peritoneal exudate cells capable of lysing P815 mastocytoma cells, a tumor cell line highly resistant to lysis by unstimulated NK cells. In vivo, Bru-Pel inhibited the formation of experimental BL6 melanoma metastases; however, there was no significant effect on the eradication of established pulmonary metastatic lesions. These results demonstrate that in addition to its previously described macrophage-activating ability, Bru-Pel is highly efficient in stimulation of NK cell-mediated cytotoxicity in mice.