The role of lymph node cells in the inhibition of metastasis of B16-BL6, a highly metastatic variant of B16 melanoma, by Lactobacillus casei YIT9018 (LC 9018) in C57BL/6 mice was determined. Subcutaneous (s.c.) injection of LC 9018 into the left inguinal or the left axillary region inhibited both axillary lymph node and lung metastasis of B16-BL6 after surgical excision of the tumors resulting from inoculation into the left front footpad of the mice. There was, however, little inhibition of the metastasis when LC 9018 was given in the inguinal or axillary region opposite the tumor inoculation. The s.c. injection of LC 9018 into the left inguinal region also augmented not only the cytolytic activity of the left inguinal lymph node cells but also the left axillary lymph node cells against B16-BL6 in vitro. However, the antimetastatic effect of LC 9018 was decreased when LC 9018 was injected s.c. into mice in which the left inguinal lymph nodes had been resected. Furthermore, natural killer cell activity of the left inguinal lymph node cells from mice injected s.c. with LC 9018 was augmented. These results suggest that the lymph node cells activated by the s.c. injection of LC 9018 played an important role in the inhibition of the metastasis and that the treatment with LC 9018 augmented the host immune response.