The role of natural killer (NK) cells in tumor growth and metastasis was studied in syngeneic normal and beige inbred C57BL/6 mice. Mice with the beige point mutation have been shown to be deficient in nonstimulated NK activity. Tumor-passaged B16 malignant melanoma cells were refractory to NK activity as determined by in vitro assay, but after in vitro culture they became sensitive to NK activity. The NK-insensitive B16 tumor grew and metastasized similarly in normal and beige mice. However, the NK-sensitive B16 tumors grew more slowly and produced fewer metastases in normal mice than in NK-deficient beige mice. Activation of NK cells by lymphocytic choriomeningitis virus infection decreased the rate of growth and number of metastases of both NK-sensitive and NK-insensitive tumors in both normal and beige mice. These results suggest the importance of NK cells as a determinant of tumor growth and metastasis.