Introduction. Detection of hepatitis C virus (HCV) has been reported in extrahepatic sites such as peripheral blood mononuclear cells and platelets. Quantitation of HCV-RNA in platelets from patients under antiviral therapy has not been reported. Material and methods. HCV-RNA levels in paired serum and platelet samples of 17 chronically HCV-infected patients were determined at baseline, week 12, end-of-treatment, and 24 weeks after completion of treatment with pegylated interferon plus ribavirin. Quantitation of HCV- RNA load was performed using COBAS® TaqMan® HCV Test v 2.0 (lower limit of detection, 25 IU/mL). The cohort predominantly consisted of female (59%) with a mean age of 50.7 ± 10.0 years. Results. Measure- ments of HCV-RNA in relation to different timepoints of therapy revealed baseline viral load was most frequently detected in higher levels in serum than in platelets (5.6 x 10 4 IU/mL vs. 379.0 IU/mL; p = 0.0002), a trend also demonstrated in most samples throughout the study. HCV-RNA was also found at low levels (< 25.0-314.0 UI/mL) persistently in platelets of three patients who have lost detectable HCV-RNA in serum during antiviral therapy, resulting in virological relapse. Conclusion. HCV-RNA levels are most frequently detected in higher levels in serum than in platelets, independent of timepoint of antiviral therapy. Further studies with an increase in size of the samples are needed to better evaluate whether or not patients who presented HCV-RNA at low levels in platelets after having lost detectable HCV- RNA in serum during antiviral therapy are at increased risk of relapse of HCV infection during follow-up evaluation.