A number of cytokines and growth factors may affect astrocyte proliferation and functions. Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic cytokine which exerts multiple effects on growth and differentiation of different cell types. TGF-beta 1 is present in low amounts in the normal brain. TGF-beta 1 gene expression, however, is increased in the central nervous system (CNS) in several pathological conditions. In this study we examined the in vitro effects of TGF-beta 1 on the proliferative response of rat astrocytes to serum and growth factors. Astrocyte cultures were established from the cerebellum and cortex of newborn Lewis rats. The proliferative response of these cultures to serum and growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), IGF-2, interleukin 1 (IL-1)] was studied by [3H]-thymidine incorporation test in the presence or absence of TGF-beta 1. TGF-beta 1 significantly inhibited the proliferative response of astrocyte cultures to both autologous and heterologous serum. In addition, a strong inhibition of bFGF-, EGF-, and PDGF-induced proliferation was observed. The effect of TGF-beta 1 on the proliferative response to IL-1 was less evident but still significant. No effect was observed when TGF-beta 1 was added to IGF-1 and IGF-2 stimulated cultures. These data confirm previous reports showing a down-regulating activity of TGF-beta on astrocyte proliferation and suggest that this cytokine may play physiological and pharmacological roles in the regulation of reactive astrocytosis in the CNS.