The activity of IL-9 on human T cells was investigated. Human T cell lines and clones, derived from PBMC by stimulation with PHA, IL-2, and irradiated allogeneic PBMC, were found to express a strong IL-9R message at the RNA level and to proliferate in the presence of IL-9, irrespectively of their CD4+ or CD8+ phenotype. Moreover, tumor-specific CTL clones also responded to IL-9. Contrasting with other T cell growth factors, such as IL-2, IL-4, or IL-7, IL-9 did not induce the proliferation of freshly isolated T cells. However, a significant proliferative response to IL-9 could be observed after a 10-day activation of PBMC with PHA, IL-2, and feeders. Taken together, our results indicate 1) that the activity of IL-9 on human T cells is wider than initially anticipated on the basis of the data obtained so far with murine cells; and 2) that proliferative responses to IL-9 require previous activation.