Five mouse oval cell lines were investigated in regards to their growth and differentiation factor (GDF) responsiveness and to changes in their GDF responsiveness following tumorigenic conversion. In all 59 GDFs and 11 comitogens were evaluated with variable responsiveness, depending on the mouse oval cell line under study, observed. Analysis of oval cell GDF responsiveness during tumorigenic conversion revealed that tumorigenic variants displayed alterations in GDF responsiveness which correlated with tumorigenicity. In addition, analysis of autocrine/paracrine growth factor production demonstrates that most tumorigenic variants produce growth factors. These studies demonstrate for the first time that (1) mouse oval cells respond to a wide variety of GDFs including various members of the interleukin, chemokine, stem cell factor, EGF, FGF, PDGF, TGF-β, VEGF, insulin, CSF, TNF, HGF, and IFN growth and differentiation factor families in addition to multiple comitogens and (2) during tumorigenic conversion mouse oval cells undergo alterations which result in both alterations in GDF responsiveness and the autocrine/paracrine production of multiple GDFs.