Post-transfusion hepatitis is still an important problem, despite the screening of blood donors for hepatitis B (HBV) and C virus infections. We assessed whether HBV DNA might be detected by PCR in prospectively collected serum samples of patients with unexplained post-transfusion hepatitis but no immunological HBV markers. We found HBV DNA in 4 (20%) of 20 patients with unexplained post-transfusion hepatitis and in 5 patients with mildly increased aminotransferases. The clinical course of these HBV infections was usually mild and self-limiting. Thus we found that low-titre, immunologically negative HBV infections do exist and might represent a significant cause of post-transfusion hepatitis.