Fibroblast growth factors (FGFs) mediate their cellular responses through specific cell surface receptors. Previous studies have indicated that acidic FGF is involved in liver regeneration and hepatic differentiation via the stem cell compartment, as well as in liver development (Marsden et al., Lab. Invest. 67:427-433, 1992). To further define the role of acidic FGF and its receptor systems in the liver, we examined the expression and cellular localization of FGF receptor-1 (flg) and FGF receptor-2 (bek) in the liver by Northern blot analysis and in situ hybridization techniques during liver regeneration, hepatic differentiation, and ontogenesis. In the normal adult liver, flg is absent in hepatocytes, whereas a low level of bek can be detected. The transcripts for bek increased, while flg exhibited little change during liver regeneration after partial hepatectomy. Both flg and bek were expressed at high levels in the developing liver. flg was expressed at a high level in embryonic liver and further increased after birth, whereas a significant increase of bek occurred at the postnatal stage of liver development. In the 2-acetylaminofluorene/partial hepatectomy model, both flg and bek are expressed at high levels during the period of active proliferation and differentiation of oval cells. In situ hybridization showed that flg was mainly localized in oval cells, whereas bek was highly expressed in both oval and Ito cells. The data suggest that bek is involved in the proliferation of mature hepatocyte proliferation during liver regeneration, while flg is characteristic of primitive hepatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)