The effect of a cloned T-cell line on the in vivo growth of syngeneic lymphoma cells was studied. 1E4 is an H-2-restricted cytotoxic T-cell clone that efficiently kills Abelson virus-induced lymphoma target cells (L1-2) at low effector/target ratios, as measured by in vitro cytotoxicity assays. In addition, it is long lived in vitro in the absence of stimulation and survives for more than 1 wk in vivo in the absence of exogenous antigen or growth factors. Mice injected intraperitoneally with lethal doses of L1-2 and then treated with 1E4 survived longer than animals treated with saline or with a control T-cell clone. Multiple weekly injections of effector cells, or a single injection in animals given a low dose of tumor cells, resulted in 50-80% long-term survivors. The observation that intravenous injection of killer cells was less effective than intraperitoneal treatment, coupled with the previous demonstration of markedly abnormal circulatory patterns for T-cell clones, suggests that those animals succumbing to progressively growing neoplasm die because the effector cells are unable to home into peripheral sites of tumor deposition. Thus, although this cytotoxic T-cell clone does have useful in vivo activity, its function may be partially limited by a generalized defect in migration.