Transforming growth factor-beta (TGF-beta) is a potent inhibitor of immune responses. Macrophage-derived products, including TGF-beta, have been suggested as inhibitors of the antitumor immune response. We hypothesized that IL-7, a cytokine with antitumor properties, may exert its immunoregulatory effects in part through the down-regulation of TGF-beta. To test this hypothesis we analyzed IL-2-stimulated murine macrophage TGF-beta mRNA expression following exposure to IL-7 both in vitro and in vivo. IL-7 down-regulated IL-2-induced TGF-beta expression by macrophages in vitro, as well as after i.p. injections of IL-2 and IL-7 in vivo. The IL-7-mediated inhibition of TGF-beta mRNA expression did not require new protein synthesis and therefore appears to be a direct effect of IL-7. IL-7 had no significant effect on the stability of TGF-beta mRNA. Nuclear run-on assays revealed that the suppression of IL-2-induced TGF-beta gene expression by IL-7 is mediated at the level of transcription. Also, IL-7 decreased TGF-beta secretion as measured by bioassay. We conclude that IL-7 down-regulates TGF-beta and suggest that some of the proliferative and cytolytic activities mediated by cells exposed to IL-7 may be caused by a decrement in macrophage-derived TGF-beta.