Lovastatin, the drug introduced recently to treat hypercholesterolemia and displaying antiproliferative activity against tumor cells in vitro, was used for the local therapy of MmB16 melanoma in mice. Female B6D2F1 mice were injected with 1 x 10(6) of MmB16 melanoma cells into the right hind limb. On the 7th day after the injection of tumor cells mice were divided into four groups and were injected with: (a) saline solution (control group), (b) TNF-alpha alone, (c) lovastatin alone, and (d) a combination of TNF-alpha and lovastatin. Statistically significant inhibition of tumor growth was observed in mice treated with both TNF (5 micrograms/day) and lovastatin (200 micrograms/day). We also observed the prolongation of survival of tumor-bearing mice after combined therapy with both TNF-alpha (5 micrograms/day) and lovastatin (1 mg/day) in comparison to all other groups. Our data suggest that lovastatin may synergistically potentiate the antitumor activity of TNF-alpha.