The effect of alpha-interferon on the hepatitis C genotypes was examined in 25 anti-HCV-positive haemophilic patients. The rate of multiple HCV genotypes in patients who are likely to have mixed infections was also studied. Pretreatment results showed that 3/25 (12%) patients had a change in genotypes, whereas posttreatment this rose to 10/25 (40%). Seven of 10 (70%) patients who showed a change in genotype had a clinical response to alpha-interferon. Six of 25 (24%) patients showed a complete clinical response to alpha-interferon, and the majority of these were either type 2 or 3. This study supports previous evidence that type 1 is less likely to respond to alpha-interferon, and that alpha-interferon may alter the concentrations of the various circulating genotypes present in multiply-infected patients. There are many difficulties in studying hepatitis C in haemophilic patients due to the sequence heterogeneity within each individual, and this study has shown that no ideal method exists as yet for looking at HCV genotypes in multiply-infected individuals.