The presence of IgM and IgA antibodies with specificity for human serum albumin (HSA) were consecutively analyzed in serum samples from four patients with biopsy verified CAH type B during seroconversion in the HBe/anti-HBe antigen system. Circulatory IgM anti-HSA antibodies were present during HBe antigenemia. The antibody titers fluctuated, decreased, and were finally lost from the circulation. After the disappearance of IgM anti-HSA antibodies, seroconversion to anti-HBe reactivity occurred and a quiescent phase of the disease was established, as judged by normalization of transaminases and absence of circulatory HBV-DNA. IgA anti-HSA antibodies persisted in the circulation after the elimination of IgM anti-HSA and seroconversion to anti-HBe reactivity. For one of the patients, a dramatic increase in titers was followed by elimination of IgA anti-HSA and seroconversion to anti-HBs. The data indicate that the host "self"-component HSA, when associated with "foreign" HBe or HBs antigenic structures, elicit immune responses to HSA, preventing the adequate development of anti-HBe and anti-HBs. The cessation of anti-HSA reactivity, however, seemed to permit subsequent sensitization to HBe and HBs antigenic determinants, as detected by the presence of circulatory antibodies.