Oral administration of forphenicinol, S-2–(3-hydroxy-4-hydroxymethylphenyl)glycine, inhibited the growth of EL4 lymphoma by both pre- and posttreatment. Although some mice given this drug rejected the tumor, they could not obtain acquired immunity against the tumor. Macrophages taken from normal mice did not inhibit the growth of EL4 cells in vivo (tumor neutralization assay) or in vitro (cytostasis assay). Forphenicinol induced effector activity in such macrophages neither in vitro nor in vivo. Forphenicinol administration to mice bearing EL4 activated macrophages to inhibit the growth of EL4 in vitro and in vivo. Moreover, it stimulated the tumor growth-inhibitory activity of splenocytes in both tumor-free and tumor-bearing mice.