Hepatitis C virus (HCV) commonly causes a chronic infection, but a minority of patients are able to clear the virus and do not run the risk of developing HCV-induced organ damage. Genetic associations between immunoregulatory cytokines interleukin (IL)-1, -6, and -10 with clinical features of HCV, including virus clearance, have been inconsistent. We determined cytokine genotypes in 606 patients who had serologic evidence of HCV exposure, 190 (18%) of whom were consistently negative for HCV RNA, indicating successful virus clearance. There was no significant difference in genotype frequencies between HCV clearance and nonclearance groups for IL-1B (-511 and +3954), IL-1A (+4845), IL-1RN (+2018), IL-6 (-174), or IL-10 (-1082). We conclude that these single nucleotide polymorphisms are unlikely to play an important, if any, role in determining the likelihood of clearing HCV infection.