Co-infection with GB virus C (GBV-C) and human immunodeficiency virus (HIV) appears to reduce mortality for HIV/AIDS. Epidemiological and demographic factors for GBV-C were examined prospectively in 167 subjects at risk for co-infection. We attempted to establish a hierarchical exposure risk for GBV-C. Overall exposure to GBV-C was 45.5%. In univariate analysis, GBV-C was associated with male to male sex (P<0.0001), HIV infection (P=0.0005) and hepatitis B infection (P=0.006). Injecting drug use approached statistical significance (P=0.08) while being a female sex worker was not associated with GBV-C exposure/infection (P=0.85). Exposure to GBV-C in 192 healthy blood donors was found to be 9.4%. In conclusion, the data suggest that male to male sex is a more effective mode of transmission of GBV-C and that GBV-C is associated with HIV co-infection. As male to male sex is also a risk factor for HIV transmission our data suggest that many may benefit from the potential protective effect GBV-C exerts on HIV-infected persons.