Persons with immune deficiency may present with atypical results in serological tests for hepatitis B virus (HBV). Frozen serum specimens that were sequentially obtained over time from a cohort of 57 HIV-infected patients, all of whom tested positive only for antibody to hepatitis B core antigen (anti-HBcAg), were therefore retested for HBV markers, including HBV DNA. The results were assessed for their time course and correlated with clinical data and alanine aminotransferase (ALT) values. Forty-eight patients were male; intravenous drug users constituted the principal risk group (n = 30), followed by homosexual men (n = 22). Thirty-three persons tested positive for antibody to hepatitis C virus (anti-HCV). During a median of 31 months from the first to the last serum, anti-HBcAg remained the sole marker of HBV infection in 98.2% of the patients. Polymerase chain reaction (PCR) to detect DNA for HBV core and HBV surface gene was positive in 126 (62.4%) and 121 (59.9%) of all 202 serum samples, respectively. Over time, HBV DNA was detected at least once in 51 (89.5%) patients. In contrast, decomplexed hepatitis B surface antigen (HBsAg) was detected at least once in 14 (24.6%) patients. Among patients positive for HBV DNA and negative for anti-HCV, eight (36.4%) of 22 had chronic hepatitis (ALT elevation > or = 6 months) that was attributable only to persisting HBV infection. Similarly, 12 (41.4%) of 29 patients positive for both HBV DNA and anti-HCV had chronic viral hepatitis, but their ALT values were significantly higher. In HIV-infected patients, anti-HBcAg as the sole serological HBV marker detected must be considered indicative of chronic HBV infection and is in part associated with chronic hepatitis and ALT elevation.