In rat liver there appear to be significant differences between lobes in the concentration of individual cytochrome P-450 isozymes (Sumner and Lodola, Biochem Pharmacol 36: 391-393, 1987). Because studies in patients often rely on small pieces of liver obtained from diverse anatomical locations, it seemed important to determine if the cytochromes P-450 were also heterogeneously distributed in human liver. Accordingly, tissue was obtained from ten different locations in a single human liver including those most commonly biopsied by percutaneous needles, and by surgeons during laparotomy. The differences observed between locations in the microsomal concentrations of carbon monoxide-binding protein (total cytochrome P-450), cytochrome b5, and NADPH-cytochrome P-450 reductase appeared to be small and were not statistically significant. Likewise, no significant differences were observed between locations in the specific content of HLp, HLp3, HLj, HLx or P450MP. However, the specific concentrations of HLd varied almost 2-fold between the microsomes and this was statistically significant in some cases (P less than 0.05). Our results suggest that, in human livers, regional differences in the content of cytochromes P-450 are generally small but may be significant for some isozymes. With the exception of HLd, tissue obtained by percutaneous or surgical liver biopsies is probably representative of the entire organ with regard to the enzymes assayed.