The introduction of screening for hepatitis C virus (HCV) by the National Blood Transfusion Service identified donors who had acquired HCV infection. We undertook a case-control study amongst blood donors in the Trent Region to determine risks for HCV infection. A total of 74 blood donors confirmed positive for hepatitis C infection and 150 age, sex and donor venue matched controls were included in the study. Fifty-three percent of hepatitis C infected blood donors reported previous use of injected drugs compared to no controls; relative risk (RR) not estimatable (lower limit 95% CI = 20). Other risk factors were a history of: receipt of a blood transfusion or blood products RR = 3.6 (95% CI 1.5-8.3), having been a 'health care worker' RR = 2.8 (95% CI 1.1-7.6), tattooing RR = 3.3 (95% CI 1.2-8.7), and an association with having been born abroad RR = 3.2 (95% CI 1.1-9.5). No risk was shown for a history of multiple sexual partners, ear piercing or acupuncture. Injecting drug use explains more than 50% of hepatitis C infections in blood donors, a group who are less likely to have injected drugs than the general population.