Parameters of immune reactivity of the tumor-resistant X/Gf mouse have been studied. X/Gf mice show better survival than do control strains following i.p. inoculation with graded doses of YAC lymphoma cells. The natural killer cell activity of X/Gf mice was higher than that of control mice, and this elevated NK activity was inherited by (C57BL/6 X X/Gf)F1 mice. Differences in NK activity of fresh spleen cells from X/Gf, C57BL/6, and (C57BL/6 X X/Gf)F1 mice were not reflected in their ability to lyse in vitro-derived, cloned, transformed cell lines from X/Gf or C57BL/6 mice in an 8 h 51Cr assay; however, the X/Gf-derived malignant cells were more sensitive to lysis than the C57BL/6-derived cells. In order to test whether X/Gf mice demonstrated any exceptional ability to recognize and destroy altered autologous cells, experiments were performed with TNP-modified syngeneic cells. While X/Gf and B10.A effector cells appeared to respond with similar magnitude, hapten-modified X/Gf cells were stronger stimulator cells and more sensitive targets than control strain cells. The ability of X/Gf mice to reject H-2 compatible and incompatible skin grafts is normal, as judged by a comparison of the rejection times with control strains. Allogeneic mixed lymphocyte reactivity, T-cell-mediated lympholysis, delayed-type hypersensitivity reactions, and in vivo phagocytosis of inert particles are of comparable magnitude in X/Gf and control strain mice.