We used an experimental murine cancer metastasis model in which a colon adenocarcinoma cell line generates lung metastases, whose growth is stimulated in response to injection of bacterial lipopolysaccharide (LPS), to investigate the role of NF-κB in inflammation-induced tumor growth. We found that LPS-induced metastatic growth response in this model depends on both TNFα production by host hematopoietic cells and NF-κB activation in tumor cells. Inhibition of NF-κB in both colon and mammary carcinoma cells converts the LPS-induced growth response to LPS-induced tumor regression. The latter response is TNFα-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-κB-deficient cancer cells.