The role of previously defined thymocyte (Thm) growth factors in interleukin (IL)-7-induced Thm growth has not been fully elucidated. Therefore, experiments were designed to examine the capacity of IL-7 to: (i) directly induce Thm proliferation in the absence of experimental and known physiologic costimulators of Thm mitogenesis, and (ii) synergize with other Thm growth factors in supporting Thm proliferation. The data indicate that IL-7 is directly mitogenic for Thm; that is, IL-7 induces Thm proliferation in the absence of experimental comitogens such as concanavalin A, phytohemagglutinin, and phorbol myristate acetate and in the presence of neutralizing antibodies to murine IL-1 alpha, IL-1 beta, IL-2, IL-2 receptor (IL-2R)(p55), IL-2R(p70), IL-4, IL-6, and tumor necrosis factor (TNF). We also tested previously described Thm growth factors, i.e., IL-2, IL-4, IL-6, and TNF-alpha, for the capacity to synergize with IL-7 in Thm growth. Our results indicate that IL-2, IL-6, and TNF-alpha, but not IL-4, synergize with IL-7 in supporting Thm proliferation. These data suggest that IL-7 functions alone and in a synergistic fashion with other cytokines to regulate Thm growth.