Peripheral blood mononuclear cells are reported to be one of the extrahepatic replication sites contributing to the persistence of hepatitis C virus (HCV) infection. Whole-blood and plasma samples from 61 individuals were compared as sources for the detection of HCV RNA. Forty-four of the individuals were receiving antiviral therapy, while 17 were treatment naïve. The quantitation of HCV RNA was done by a sensitive in-house real-time reverse transcription-PCR. When the viral loads in the two types of samples were compared, a correlation coefficient of 0.858 (P < 0.001) was found, indicating that plasma and whole blood are equally acceptable sources for testing for HCV RNA.