Background: Previous studies have indicated that Tec tyrosine kinase is differentially expressed in the regenerating liver. The purpose of the present study was to further investigate the potential involvement of Tec tyrosine kinase in hepatocyte proliferation and liver regeneration. Methods: Tec kinase gene expression after partial (two-thirds) hepatectomy was examined by representational difference analysis. Tissue distribution and potential involvement of Tec kinase in liver regeneration and hepatocyte proliferation were then determined by northern blotting, reverse transcription-polymerase chain reaction (RT-PCR), and western blotting. Full-length rat Tec cDNA was cloned. Results: Using this cDNA as the probe, northern blotting showed that Tec was specifically expressed in liver and kidney, the highest expression of Tec being detected in embryonic day 15-19 fetal livers. In contrast, the expression level of Tec in adult and neonatal rat livers was significantly decreased. Similar results were obtained from western blotting analyzes. It was thus hypothesized that Tec might be involved in hepatocyte proliferation. To test this hypothesis, Tec expression was examined in regenerating rat livers. An increase in Tec expression and activation of Tec kinase were observed within 1 h after partial hepatectomy. Moreover, it has been shown that hepatocyte growth factor (HGF) dramatically induces Tec expression in primary rat hepatocytes. Additionally, it was observed that Tec gene expression in serum-starved liver tumor cell line HepG2 was substantially decreased. Stimulation with 10% fetal bovine serum and insulin but not epidermal growth factor resulted in dramatic elevation of Tec expression in these cells. Conclusion: Tec is an inducible early response gene that might enhance hepatocyte proliferation and liver regeneration.