To establish the mechanism of progression to chronicity of the HBsAg-associated delta infection, serum hepatitis B virus and delta markers were tested in five babies born to HBsAg-positive mothers with anti-delta, in 42 follow-up patients with acute hepatitis B virus and delta hepatitis, and in collections of sera from 8 HBsAg carriers with anti-delta. Evidence of delta infection was found in the baby born to a mother with serum HBeAg and in none of the four babies born to mothers with anti-HBe. Hepatitis was self-limited in the 42 patients acutely infected by hepatitis B virus and delta agent; none developed persistent HBs-antigenemia and the majority displayed transient anti-delta of IgM class. In seven HBsAg carriers high titers of anti-delta developed during the follow-up; coincident with the rise of the antibody, aminotransferase elevation occurred in five previously asymptomatic carriers and persisted in three of them. No sign of infectious hepatitis B virus replication was detected in five of the carriers throughout the follow-up, and all of them had anti-HBe before the rise of anti-delta and of aminotransferase. HBsAg carriers with diminished hepatitis B virus synthesis appear to be at high risk of developing chronic delta infection and disease when exposed to the delta-infectious serum of other carriers.