Hepatitis C virus (HCV) is an RNA virus in the Flaviviridae family. It displays lymphotropism in addition to hepatotropism and extrahepatic manifestations are very well known. There are many studies showing an association between HCV infection and non-Hodgkin's lymphomas (NHL). In this study the evidence for HCV infection was studied in cases with NHL. To this end, anti-HCV antibody and HCV-RNA were screened in serum samples of cases with NHL using third-generation ELISA and RT-PCR. Anti-HCV antibody was studied in 223 patients and was found to be positive in 18 cases (8.1%). Anti-HCV antibody positivity was compared with our blood bank / blood donor population. There was an important increased risk of HCV infection-the common odds ratio was 34.56 and corrected odds ratio was 19.07. HCV-RNA was studied in 67 of 223 serum samples. HCV-RNA was found to be positive in 21 of 67 samples (31.3%). When compared with clinico-demographic parameters for anti-HCV and HCV-RNA, including age, nodal status, and grade (in evaluable cases), except age in cases with or without HCV-RNA, we did not find an important correlation with HCV status and clinical findings (P = 0.155; 0.442; 0.288 for anti-HCV and 0.027; 0,558; 0.126, respectively). These results suggest that HCV infection may be an important risk factor for lymphomagenesis and HCV-RNA is more useful for the detection of HCV infection in these immunosuppressed cases. Simultaneous detection of anti-HCV and HCV-RNA will be more informative in this population. (C) 2003 Wiley-Liss, Inc.