3-Methylthiopropyl (MTPITC) and 5-methylthiopentyl isothiocyanate (MTPeITC), natural compounds found in human diets, were assayed for an inhibitory activity against the growth of B16-F10 murine melanoma cells in culture. MTPITC and MTPeITC showed a potent cytostatic effect; the two agents exhibited median inhibitory concentrations of 48 and 170 nM, respectively. Oral administration of 10 mumol MTPeITC on Day 1 after intravenous tumor cell injection achieved a marked reduction of pulmonary colonization in syngeneic mice. However, it caused atrophy of the thymus and selective loss of CD4+CD8+ cells in thymocytes. On the other hand, treatment with MTPITC showed no influence on pulmonary metastaticity or thymocytes. Neither MTPITC nor MTPeITC caused significant changes in the responsiveness of the splenocytes and thymocytes to mitogen. These results suggest that MTPeITC can protect against metastaticity as well as cell growth of tumor cells, regardless of the disadvantageous action on the thymus.