The prevalence of persistent hepatitis delta (HD) antigenaemia and associated factors in patients with chronic infection with the hepatitis delta virus (HDV) were investigated. Among 157 consecutive patients known to be carriers of hepatitis B surface antigen (HBsAg), 36 (23%) had one serum marker of HDV infection (anti-HD and/or HDAg). Nine of the patients with an HDV marker were HDAg positive, including three who were anti-HD negative. A follow-up over a mean period of 13 months showed that five of five patients had a persistent HD antigenaemia. This serological profile was associated with the presence of antibody to the human immunodeficiency virus (anti-HIV) (P < 0.01), serum HIV antigen (HIVAg) (P < 0.2), and the female sex (P < 0.05). Persistent HD antigenaemia could be the consequence of the suppression of T cell cytotoxic activity against hepatocytes expressing HDAg, a lower humoral response, and/or hormonal factors.