Portal fibroblasts (PF) are a newly isolated population of fibrogenic cells in the liver postulated to play a significant role in early biliary fibrosis. Because transforming growth factor-β (TGF)-β is a key growth factor in fibrosis, we characterized the response of PF to TGF-β. We demonstrate that PF produce significant amounts of TGF-β2 and, unlike activated hepatic stellate cells (HSC), express all three TGF-β receptors and are growth inhibited by TGF-β1 and TGF-β2. Fibroblast growth factor (FGF)-2, but not platelet derived growth factor (PDGF), causes PF proliferation. These data suggest a mechanism whereby HSC eclipse PF as the dominant myofibroblast population in biliary fibrosis.