Twenty of 22 hepatitis delta virus (HDV)-superinfected chronic hepatitis B carriers who had detectable HDV RNA at the acute stage progressed to chronicity, while only 6 of 16 patients without HDV RNA did so (P less than .005). The poor outcome of patients with persistently positive or fluctuating HDV RNA has been indicated by the following findings: 24 of 38 patients suffered from prolonged hepatic inflammation complicated by three to eight episodes of exacerbations; among them, 5 developed cirrhosis and 2 died in a follow-up period of 4 years. For most patients, the replication of HBV was suppressed at acute stage; only 3 of the 38 cases had detectable HBV DNA in sera. While reactivation of HBV was found in another 8 patients in the follow-up period, for 5 it was in the presence of serum HDV RNA and 2 developed cirrhosis. Therefore, serial assays of serum HDV RNA and HBV DNA appeared to be of value in monitoring the clinical course and outcome of acute HDV superinfection and in the study of the long-term interactions between these two viruses.