Hepatitis C virus (HCV) 1a, 1b, 2a, and 2b subtypes have been studied in 30 serum samples and in 20 paired liver biopsies from children with chronic hepatitis C. One serum sample was negative to the four HCV subtypes studied. HCV 1b was detected alone in 53.3% (16/30) of the serum samples; HCV 1a alone in 23.3% (7/30) and a mixed infection in 20% (6/30). In liver samples, HCV mixed infection was detected in a significantly higher proportion (50%: p < 0.05) than in serum, whereas HCV 1b was detected alone in 35% (7/20) and HCV 1a alone in the remaining 15% (3/20) of liver samples. These results suggest that serum HCV genotyping may not reflect the viral population infecting the liver of a given patient. Additional studies should be performed concerning the pathobiology of hepatitis C virus with relation to the subtypes detected in liver.