Fibroblast growth factor (FGF)-2 is an established neurotrophic factor for dopaminergic (DAergic) neurons in the ventral midbrain. Its survival and differentiation-promoting effects on DAergic neurons in vitro and in vivo are crucially dependent on the presence, numerical expansion and maturation of astroglial cells. We show now that transforming growth factor (TGF)-beta, an established trophic factor for DAergic neurons and product of astroglial cells, mediates the trophic effect of FGF-2 on DAergic neurons cultured from the embryonic rat midbrain floor. Antibodies to TGF-beta that neutralize the isoforms -beta1, -beta2 and -beta3 abolish the trophic effect of FGF-2. FGF-2 increases TGF-beta3 mRNA and amounts of biologically active TGF-beta determined in a mink lung epithelial cell assay in a time-dependent manner. FGF-2 also induces levels of active TGF-beta in neonatal rat astrocytes cultured from midbrain, striatum and cortex. We conclude that TGF-beta is required for mediating the survival promoting effect of FGF-2 on DAergic and, possibly, cortical and striatal neurons grown in the presence of glial cells.