Pre-S2 protein in 78 samples of liver from patients with various types of hepatitis B was determined by immunohistochemical method.45 out of 78 samples (57.69%) were positive for pre-S2.The location and expression patterns of pre-S2 were similar to those of HBsAg,i.e.,pre-S2 was found in cytoplasm of hepatocytes,epithelial cells of bile ducts,and hepatocellular carcinoma cells,etc,Four different patterns diffuse,inclusion,submembranous,and membranous type were demonstrated.The membranous expression of pre-S2 was often associated with activity of liver diseases.The positive rate of pre-S2 was significantly higher in HBcAg positive group than HBcAg negative group.It seems that pre-S2 protein of HBV may be a replicative marker of HBV.