Although the possibility of sexual transmission of the hepatitis C virus (HCV) remains controversial, little is known of the associations ofpositive semen specimens with potential demographic and behavioral risk factors. Knowledge of these predictors may suggest factors that increase risk of HCV RNA in the semen. Semen and bloodfrom 80 HCV-infected homeless men were evaluatedfor the presence of HCVRNA by means of branch DNA and transcription-mediated amplification analyses. Associations of selected demographic and behavioral characteristics of the participants with presence or absence of HCV in their semen were also assessed. HCV RNA was detected in the semen of 36% of the sample. Associations were found with HCV RNA in semen and older age, higher viral loads of HCV in blood, current alcohol and lifetime methamphetamine use, and having been vaccinated for the hepatitis B virus. Findings suggest that sexual transmission of HCV is plausible and shed light on the need to conduct more in-depth investigations.