The frequency of class II human leukocyte antigen (HLA) alleles in 112 infected patients of Hispanic ancestry with serology positive for hepatitis C virus (HCV) was investigated. Our studies failed to demonstrate significant association between class II HLA alleles and the outcome of HCV infection: chronic viremia versus spontaneous viral clearance. Our results suggest that the genes responsible for the outcome are unknown, so far, and those HLA associations reported in several ethnic groups may represent genetic markers in nonrandom association with the responsible genes involved in determining viral clearance or chronic viremia following HCV infection.