To detect hepatitis D virus (HDV) RNA in asymptomatic HDV-infected risk groups, Northern blot hybridization was carried out using a strand-specific riboprobe. Univariate and multivariate analyses were carried out to evaluate factors associated with HDV viremia and elevated transaminase levels in these subjects. Two (15%) of 13 antibody to HDV (anti-HDV) -positive intravenous drug addicts, 15 (33%) of 45 anti-HDV positive prostitutes, and 6 (40%) of 15 anti-HDV positive brothel goers had detectable serum HDV RNA. Older age (> 31 years old) was negatively associated with HDV RNA (P < .04), while hepatitis B e antigen (HBeAg) was positively associated with it (P < .002) in univariate analysis. Only HBeAg was still significant in multivariate analysis (P < .05). Of the 76 asymptomatic anti-HDV positive case, 28 (37%) had mildly elevated serum ALT levels and only 5 (7%) had ALT levels more than twice normal (> 80 U/L). HBeAg (P < .05) and HDV RNA (P < .02) were two factors associated with ALT elevation in univariate analysis, and HDV RNA was the only significant factor in multivariate analysis (P < .005). In summary, active replication of HBV seemed to be of help for the assembly of HDV and viremia. However, active replication of HDV was associated mostly with mildly elevated ALT levels in these subjects. These cases may represent a particular group in the disease spectrum of HDV infection.