Hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are primary mitogens for hepatocytes in culture. hepatocytes express the HGF-receptor MET but not HGF itself. To investigate the influence of autocrine HGF expression on the proliferative potential of hepatocytes, primary cultures were submitted to retrovirus-mediated transduction of the human hgf (huHGF) cDNA. Expression of the transduced cDNA revealed a minimum 2-fold increase in HGF-mRNA, whereas expression of the Escherichia coli beta-galactosidase gene remained even. Estimation of huHGF copy numbers showed there was a minimum 4-fold increase, suggesting an increase in the population of transduced cells. Immunoprecipitation of excreted huHGF and growth bioassays proofed that HGF was present and functional. HGF is excreted into the medium and therefore, by diffusion, available to transduced and non-transduced cells. The increase in huHGF-transduced cells suggests that the autocrine pathway as opposed to the paracrine pathway, which are both present at the same time, confers a growth advantage to these cells.