The rate of HBeAg clearance and the outcome were analyzed in 46 patients with asymptomatic chronic hepatitis B virus (HBV) infection whose condition was followed for 1-4 yr (mean 2.4). Mean age was 32.5 yr (range 10-68), and 28 (61%) were males. All had chronic hepatitis, on biopsy, and were positive for HBcAg on hepatocytes. Alcoholics, homosexuals, drug abusers, immunocompromised patients, and those with advanced liver disease were excluded. During the follow-up, 25 patients (54%) cleared HBeAg and became seronegative for HBV-DNAp. The estimated annual rate of seroconversion was 26%. One patient cleared HBsAg. After seroconversion, 18 patients had no evidence of ongoing liver disease, proved by biopsy in eight and by clinical follow-up in 10 that refused biopsy. A second liver biopsy was available in 15 patients, and HBcAg was negative in all; histology was normal in eight, unchanged in one, and compatible with cirrhosis in six. All six had clinical and/or biochemical evidence of advanced liver disease. These were significantly older at the start of the study, and had chronic active hepatitis with bridging necrosis on initial biopsy. Early identification of patients with silent chronic HBV infection and high levels of viral replication for antiviral therapy could prevent transmission of the infection and stop progression to liver cirrhosis and hepatocellular carcinoma.