We have investigated 38 hepatitis B surface antigen (HBsAg)-positive and 34-negative patients with acute and chronic liver disease for the presence of hepatitis B virus (HBV) DNA in peripheral mononuclear blood cells. Among the HBsAg-positive subjects HBV DNA was detected in the mononuclear cells of asymptomatic HBV carriers (2/6), patients with acute hepatitis (8/8), chronic active hepatitis (18/21), and with hepatocellular carcinoma (2/3); the viral DNA sequences were also identified in the mononuclear cells of patients with HBsAg-negative acute hepatitis (2/3), chronic active hepatitis (5/15) and hepatocellular carcinoma (5/16), some of these showing no evidence of HBV by conventional serological markers. By contrast HBV DNA was not detected after resolution of the acute viral infection. For 7 patients different mononuclear cell-enriched subpopulations were assayed and the viral DNA was observed in T lymphocytes (both OKT4+ and OKT8+ enriched subsets) and/or in B enriched lymphocytes; the restriction DNA patterns showed in some patients a genetic organisation of the viral DNA similar to those observed in the liver (including free monomeric and oligomeric HBV DNA and results consistent with integrated viral sequences); however, no HBV DNA replicative forms were detected. These results show that the hepatitis B virus infection of mononuclear blood cells (including lymphoid cells) is a frequent event at all stages of the viral infection which might be related to immunological abnormalities observed in HBV carriers; in addition the mononuclear blood cells analysis may provide an insight to the liver cells status.