ABSTRACT— During a prospective follow-up study of 65 children with chronic hepatitis B, the HBcAg expression pattern in the liver was investigated, by immunofluorescence, in relation to biochemical and histological features and to the evolution of the disease. HBcAg was detected in 50 (77%) cases, with a diffuse pattern of distribution (more than 60% positive nuclei) in 20 cases, and with a focal pattern (less than 40% positive nuclei) in 30 cases. The diffuse pattern significantly prevailed in younger children, while the focal pattern was more frequent in children beyond 10 years of age. Transaminase levels were higher and histological features of activity were more frequent in patients with the focal pattern than in those with a diffuse pattern. Twenty-five hepatitis B e antigen (HBeAg) positive children, all initially HBcAg positive, were followed prospectively for 24 months. Seroconversion to anti-HBe, with subsequent normalization of transaminases, occurred in 72% of cases with a focal pattern, but only in 21% of those with a diffuse HBcAg pattern. In four patients transition from the diffuse to the focal pattern was observed during follow-up. These results suggest that, in children with chronic hepatitis B, the diffuse HBcAg pattern in the liver might reflect an earlier phase of infection. In HBeAg positive cases the focal HBcAg pattern may represent a prognostic marker of short-term favourable evolution of the disease.