In order to separate graft-versus-leukemia (GVL) effect from graft-versus-host (GVH) reactions in allogeneic cell therapy, we established cytotoxic T cell lines (CTL) against irradiated A20, WEHI-3 and PU cells, ie cells from 3 hematopoietic tumors of Balb/c origin. Immunization with these cell lines did not lead to prolonged survival in Balb/c mice. The cytotoxic activity of the CTL was tested against the 3 leukemias. In all 9 combinations the highest specific lysis was achieved against the stimulating tumor. Cold target inhibition experiments showed that the activity against 51Cr-labelled leukemia cells could be almost completely inhibited by adding a sufficient amount of unlabelled target cells. On the other hand, when unlabelled concanavalin A-induced Balb/c blast cells were added, the inhibition was incomplete. By means of flow cytometry it was excluded that the different susceptibilities and inhibitory potentials of tumor cells and nonmalignant blasts are caused solely by differences in the MHC expression of the target cells. These findings confirm that allogeneic CTL are capable of discriminating malignant from nonmalignant cells, even if the tumor is nonimmunogenic in syngeneic animals.