Sixty-two anti-HCV and HCV-RNA positive Swedish blood donors (44 men, 18 women; median age 34 years) were studied. HCV genotypes were correlated to parenteral risk factors, liver morphology, serum alanine aminotransferase (ALAT) levels and HCV antibody profile. Forty percent of the donors were infected with HCV genotype 1a, 10% with 1b, 21% with 2b, and 29% with 3a. Intravenous drug use (IVDU) was more common in donors with genotype 3a than in those with genotype 1a (p = 0.024), and prior blood transfusion more common in genotype 2b than in 3a (p = 0.012). Chronic active hepatitis with and without cirrhosis was found in 38% of donors infected with genotype 2b as compared to 8% of donors infected with 1a (p = 0.034). Forty percent of donors with genotype 1a had normal ALAT at the time of liver biopsy versus 11% with genotype 3a (p = 0.046). Antibodies to C33c and C22-3 were present in nearly all donors whereas reactivity to C100-3 and 5-1-1 was detected more often in donors with genotypes 1a and 1b as compared to donors with genotypes 2b and 3a. In conclusion, genotype 3a was correlated to IVDU or tattooing as parenteral risk factors for the acquisition of HCV infection, and genotype 2b to prior blood transfusion. Donors with genotypes 1a seemed to have less severe liver disease than those infected with genotypes 2b and 3a.