Several studies have suggested an association between hepatitis C virus (HCV) and low-grade B-cell non-Hodgkin's lymphomas. The results, however, have been controversial. Italian and Japanese studies have reported a 40% prevalence rate, but the data were not confirmed by English and Canadian studies. We evaluated the prevalence of HCV infection in 109 patients with non-Hodgkin's lymphomas, and compared it with a control group composed of 67 patients with Hodgkin's disease and 31 patients with chronic lymphocytic leukemia. The prevalence of HCV infection was also determined in blood donors. HCV infection was detected using second and third generation anti-HCV ELISA. Positive results were additionally confirmed using Inno-LIA AbIII and/or RNA-HCV by PCR. Immunohistochemical stains were used to determine B or T cell lineage when the morphological analysis was not sufficient for lymphoma classification. HCV infection was detected in 9% of patients with non-Hodgkin's lymphomas, in 2% of patients in the control group (p=0.036), and in 1.2% of blood donors. There was no difference in the prevalence of HCV infection between patients with B or T cell lymphomas. Blood transfusions or previous surgeries, both risk factors for HCV infection, were detected in 90% of the patients with a positive anti-HCV test, in average 17 and 36 years before the diagnosis of lymphoma, respectively. Seventy percent of the patients with non-Hodgkin's lymphomas and a positive anti-HCV test presented evidence of chronic liver disease when the lymphoma was diagnosed. This study suggests the presence of an association between HCV infection and non-Hodgkin's lymphomas in Brazil.