Positivity of recombinant immunoblot assay (RIBA) for detection of antibodies to hepatitis C virus (anti-HCV) is usually associated with HCV viremia. The significance of an indeterminate RIBA result, defined by reactivity to only one HCV antigen, is unclear. Whether anti-human immunodeficiency virus (HIV)-negative or -positive subjects with an indeterminate RIBA have HCV viremia detectable by polymerase chain reaction was investigated. An indeterminate RIBA was found in 48 (15%) of 318 anti-HIV-negative and 38 (23%) of 167 anti-HIV-positive subjects (P < .05). Clinical stage was IV-C-1 or IV-C-2 in 82% of those anti-HIV-positive. HCV viremia was found more frequently in anti-HIV-positive (89%) than in anti-HIV-negative subjects (50%) with an indeterminate RIBA (P < .05). These results suggest an impaired anti-HCV response associated with HIV infection.