Hepatitis C virus (HCV) is a major etilogical agent of post-transfusional and sporadic acute and chronic hepatitis in various geographical areas. However, anti-HCV seroconversion was uncommon in a recent study of patients with post-transfusional hepatitis in Paris, France (N. Asar et al., companion paper). The aim of the present study was to detect viral markers, in particular HCV RNA and hepatitis B virus (HBV) DNA, in these patients. A combination of second-generation assays for anti-HCV antibodies and the polymerase chain reaction were used to identify HCV RNA and HBV DNA sequences in serum samples collected before and after transfusion from patients who developed non-A, non-B hepatitis. Eighteen cases of acute, post-transfusional, non-A, non-B hepatitis were identified in the prospective clinical survey. Only three of these 18 subjects developed anti-HCV antibodies in second-generation tests. HCV RNA was identified in the serum of these three subjects but in none of the others. Two patients who were anti-HCV-negative had polymerase chain reaction evidence of HBV DNA. Known viral markers were not identified in 13 of the 18 patients with acute post-transfusional non-A, non-B hepatitis. These results raise the issue of HCV strains or 'non-A, non-B, non-C' viruses not identified by current HCV and HBV markers and implicated in post-transfusional hepatitis in France.