Egypt has the world's highest prevalence of infection with hepatitis C virus (HCV), which is a major cause of hepatocellular carcinoma. The high HCV prevalence is largely attributed to the parenteral antischistosomal therapy (PAT) campaigns conducted from the 1950s through the 1980s; however, the primary modes of transmission in the post-PAT period are not well known. In this study we examined the associations between HCV prevalence and exposures to risk factors, including PAT, in a high HCV prevalence population. Using a cross-sectional design, we examined the associations between demographic characteristics and risk factors for HCV transmission and HCV positivity prevalence among a sample of Egyptian residents. Data were collected through an interview-administered survey, and the association estimates were determined using χ (2) and logistic regression. The highest HCV positivity prevalence was observed in cohorts born before 1960, and declined precipitously thereafter; whereas the proportion of subjects reporting PAT remained relatively stable. Being male, having a rural residence, and having received PAT were all associated with HCV positivity; however, PAT alone could not account for the high prevalence of HCV. In Egypt, PAT and other transmission factors yet to be identified, as well as cohorts born before the 1960s and infected with HCV, are most likely the main contributors to the current HCV endemic.