Hepatitis C virus (HCV) has been suggested to play an etiological role in the development of B-cell non-Hodgkin's lymphoma (NHL) in Italy. However, another study in Scotland questioned increased risk of development of NHL in patients with chronic HCV infection. A total of 2,162 patients admitted to 3 hospitals in Osaka, where the incidence of HCV-related hepatitis is highest in Japan, during the period from 1957 to 1997 were followed up from the date of diagnosis of chronic HCV-related hepatitis until 30 October 1997. Overall, 12,404.5 person-years of observation were accrued with a follow-up period ranging from 0.25 to 40.4 (average 5.74) years. NHL of the B-cell type developed in 4 patients. The interval between onset of chronic HCV and NHL ranged from 6 to 36 (median 13) years. Expected number of cases of NHL in the sex-, age- and calendar year-matched general population was 1.90, which gave a relative risk (RR) of 2.10 (95% confidence interval 0.57-5.38; p = 0.247). Taking the much higher RR for hepatocellular carcinoma among patients with HCV infection into account, chronic HCV infection was considered to be moderately associated with increased risk of NHL.