Most hepatitis C occurs among young adults with high-risk behaviors or lifestyles. Although the most efficient transmission of HCV is through large or repeated percutaneous exposures to infectious blood, transmission also seems to occur through occupational exposure, sexual activity, household contact, and perinatal exposure. The risk of transmission in these settings is most likely dependent on the titer of virus as well as the type and size of the inoculum and the route of transmission. The apparent inconsistency of results between studies is probably a result of the small sample sizes, in that insufficient numbers of infectious persons are included, as well as the variations in methodology and serologic testing. Although HCV may be inefficiently transmitted by inapparent parenteral or mucosal exposures, the high rate of persistent infection with HCV creates a large reservoir of persons who are infectious to others. Current preventive measures, such as donor screening, prevent only a small proportion of the disease. Epidemiologic studies to define the risk of, and the factors facilitating transmission of HCV in other settings, still need to be conducted to develop measures to prevent most disease acquisition.