Two methods were used to unveil a possible previous hepatitis B virus (HBV) infection in patients with postnecrotic liver cirrhosis. The anamnestic response to a booster injection of HB vaccine was assessed, and the polymerase chain reaction (PCR) technique for the detection of HBV-DNA in serum and liver tissue, using primers to span the precore and core regions, was employed. Seventeen patients with postnecrotic liver cirrhosis were selected from a population with a high prevalence of HBV infection and were compared with 11 liver cirrhosis patients who were positive for antibodies to surface antigen (anti-HBs) IgG antibodies. All patients were given one dose of HB vaccine into the deltoid muscle, and anti-HBs titers were measured 1 and 4 wk after injection. Three of 17 patients, initially negative for anti-HBs, showed a primary response, with titers of anti-HBs rising from 0 to a maximum of 85 mIU/ml after 4 wk; the rest had no response. Of the 11 patients positive for anti-HBs, of whom nine were also IgG anti-HBs positive, only four had an intense anamnestic response, with anti-HBs titers rising to more than 10 times the initial values (up to 10,800 mIU/ml). Serum HBV-DNA was detected in eight patients in the antibody-negative group and in only one patient in the antibody-positive group (p less than 0.02). None of the four patients with positive anamnestic response had HBV-DNA in the serum. The prevalence of HBV-DNA in the liver was similar in both groups. Absence of HBV-DNA in serum of most patients positive for anti-HBs supports the hypothesis that HBV particles released from the liver may be captured by antibodies in the serum. We conclude that assessment of the anamnestic response to HB vaccine has no diagnostic advantage, compared with direct measurement of conventional HBV serological markers in patients with liver cirrhosis. Moreover, we suggest that this type of immunologic response may not occur when virion-associated HBV-DNA is present in the serum.