Serum hepatitis B core antigen (HBcAg) was investigated in 85 patients with chronic hepatitis B virus (HBV) infection using a modified radioimmunoassay technique, based on high molarity treatment of samples to avoid masking of the antigen by the excess homologous antibody. Eighty-eight percent of HBeAg-positive cases and 19% of anti-HBe-positive cases were HBcAg positive in serum, with a positive correlation with the presence of HBcAg in the liver. Although the sensitivity of the method for the presence of complete virions was not absolute, as shown by the comparison with serum HBV-DNA testing, this technique may be helpful for assessing virus synthesis in patients with HBV infection.