Macrophage inflammatory protein 1α (MIP-1α), a CC chemokine, is a chemoattractant for T cells and immature dendritic cells. Plasmacytoma cells expressing MIP-1α generate a cytotoxic T cell response without affecting tumor growth. To understand this discrepancy, we compared a local tumor model with a metastatic one using MIP-1α-transfected B16 F10 melanoma cells. Clonal idiosyncrasies were controlled by selecting three lipotransfected tumor clones and two pcDNA vector transfected control clones with equivalent in vitro proliferative capacities. No significant differences were seen between the MIP-1α-producing and control melanoma cells after sc injection in the hind leg. All animals had a leg diameter of 10 cm in 18.5–21.5 days. However, after iv injection the number of pulmonary foci was significantly reduced in the MIP-1α-producing clones. Injection of 10 6 control transfected cells resulted in a median of 98.5 tumor foci in 2 wk, whereas the injection of the MIP-1α-producing clones resulted in 89.5, 26.5, and 0 foci. The number of metastatic foci was inversely proportional to the amount of MIP-1α produced by the clone in vitro. Flow cytometry showed a significant increase in CD8+ cells in lungs of mice with MIP-1α-transfected tumors 3 days after injection. This increase was not maintained 10 days later despite continued production of MIP-1α. The protection offered by transfection with MIP-1α was significantly impaired in β 2-microglobulin−/− mice. Our findings suggest that MIP-1α is effective in preventing the initiation of metastasis, but not at sustaining an effective antitumor response.