Thymus-derived lymphocytes (T cells) are thought to play an important role in the recognition and destruction of neoplastic cells in the host. This principle has provided a foundation for the establishment of therapy with T-cell-stimulating lymphokines, notably interleukin-2, as an approach to the eradication of certain malignancies. Another lymphokine, B-cell-stimulatory factor-1 (BSF-1), also known as IL-4, has also been shown to be capable of inducing T-cell proliferation and cytolytic activity in vitro. We demonstrate herein that in immunosuppressed mice, in vivo IL-4 administration enhances the ability of treated animals to generate cytotoxic T lymphocytes directed against an allogeneic tumor challenge. Moreover, IL-4 is approximately 25 times more effective, on a weight basis, than is IL-2 in augmenting cytotoxic T-lymphocyte activity. This difference in efficiency between the two lymphokines may be partly due to the in vivo half-life. We have found that IL-4 has a serum half-life of 19 +/- 2 min following intravenous administration, in contrast to the half-life of IL-2, which has been reported to be 3.7 min +/- 0.8. These results are not only of interest for our basic understanding of the physiological role of IL-4 but may have immediate importance in clinical settings where lymphokine therapy is contemplated.