The antimetastatic effects of MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide (MDP), against three different types of highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 T lymphoma, were examined in C57BL/6, Balb/c and CDF1 mice, respectively. The administration of 100 micrograms of MDP-Lys(L18) 2 or 4 days before tumour inoculation led to a significant decrease in lung metastasis of B16-BL6 melanoma or colon 26-M3.1 carcinoma cells. MDP-Lys(L18) was also effective in the inhibition of liver metastasis of L5178Y-ML25 lymphoma cells by administration 2 or 4 days before tumour inoculation. The prophylactic effect of 100 micrograms of MDP-Lys(L18) on tumour metastasis was evident for the different administration routes, i.e. subcutaneous, intravenous or intranasal injection, or oral administration. It is of prime interest that oral administration of 1 mg of MDP-Lys(L18) induced a significant decrease in lung metastasis of B16-BL6 melanoma cells. Administration of MDP-Lys(L18) 4 days before assay led to induction of tumoricidal activity by peritoneal macrophages and growth inhibition by the sera against B16-BL6 or L929 cells. When MDP-Lys(L18) was subcutaneously administered five times after tumour inoculation to test therapeutic effect in an experimental and spontaneous metastasis model using B16-BL6 melanoma, the consecutive administrations of MDP-Lys(L18) significantly inhibited lung metastasis in tumour-bearing mice. These results suggest that MDP-Lys(L18) is able to enhance host resistance to reduce tumour metastasis and is a potent immunomodulating agent which may be applied prophylactically or therapeutically for the treatment of cancer metastasis.