Normal murine spleen cells were sensitized to syngeneic myeloid leukemia cells by RNA extracted from the lymph nodes and spleens of Hartley guinea pigs immunized with the murine leukemia cells. Sensitization mediated by RNA was an active process that required physiologic temperature and at least a 10-minute incubation. RNA extracted from unimmunized guinea pigs of guinea pigs immunized with normal spleen cells failed to sensitize the mouse spleen cells. Sensitization was specifically directed toward leukemia cells, whereas the spleen cells remained unreactive toward normal spleen or bone marrow cells. The sensitizing moiety was RNA itself inasmuch as it was inactivated by RNase and not by DNase or pronase. Preparations whose RNA patterns on sucrose density centrifugation gave evidence of degradation of the RNA did not sensitize normal spleen cells. These studies demonstrate that xenogeneic immune RNA can specifically sensitize normal spleen cells to syngeneic myeloid leukemia cells.