Hepatocytes of the right and left lobes of the fetal liver are surrounded by different microenvironments. The right and left lobes of the fetal liver are perfused by vascular systems carrying different concentrations of oxygen and constitute distinct functional units. The aim of this study was to assess the expression of the phenobarbital-inducible cytochrome P-450 b,e genes in hepatocytes of the right and left fetal liver lobes in mice. Northern-blot analysis using [32P]cDNAs and quantitative dot-blot hybridization were performed to assess the size and levels of these mRNAs in the right and left fetal liver lobes. In fetal mice, the levels of cytochrome P-450, b,e mRNAs were higher in the left than in the right fetal liver lobe. During the last days of gestation and in the immediate postnatal period, the levels of liver cytochrome P-450 b,e mRNAs increased predominantly in the left liver lobe. In contrast, the levels of albumin and alpha-fetoprotein mRNAs (genes studied to assess the specificity of these findings) were similar in each of functional units of the fetal liver. Phenobarbital induction of cytochromes P-450 b,e mRNAs was not observed in either of the fetal liver lobes. Postnatally, phenobarbital induced these cytochromes similarly in the right and left liver lobes. Therefore, the microenvironment surrounding fetal hepatocytes seems to influence the expression of the cytochrome P-450 b,e genes. This lobar heterogeneity of expression disappears as the pattern of adult liver circulation is attained.