Transforming growth factor-beta 1 (TGF-beta 1) markedly increased the mRNA encoding nerve growth factor (NGF) in cultured rat astrocytes in a time- and concentration-dependent manner. The maximal effect of TGF-beta 1 (a 50-fold increase in NGF-mRNA) was reached after 24 h incubation. The TGF-beta-mediated increase in NGF-mRNA results from enhanced transcription as shown in nuclear run-on studies and in transfection assays using the NGF promoter linked to a chloramphenicol acetyltransferase (CAT) reporter gene. TGF-beta 1 also increased its own expression in astrocytes as well as that of the proto-oncogene c-fos. Intraventricular injection of TGF-beta 1 resulted in an increase of NGF-mRNA levels in the rat hippocampus (3-4 fold) showing that TGF-beta 1 is also effective in increasing NGF expression in vivo.