I agree with Romeo and colleagues [1] that testing liver biopsy specimens for hepatitis C virus (HCV) RNA is useful in monitoring therapy for HCV infection, but their conclusion is incorrect. They claim that a polymerase chain reaction (PCR) assay that is negative for HCV RNA in a liver biopsy specimen indicates eradication of the virus. As the authors indicated, the sensitivity of their PCR assay is 5 x 10⁴ HCV particles/mL of serum, which is the limit of sensitivity of the assay because of the inefficiency of the reverse transcriptase step in the method. Thus, approximately 10⁴ particles/mL may still be present with a negative assay result. At present, no method can exclude residual HCV infection. Until a method for detecting a single molecule of HCV RNA is developed, the end point for therapy should be the absence of HCV RNA in the blood by PCR assay and the absence of HCV RNA in the liver by PCR or preferably by in situ hybridization. The patient must then be carefully monitored for relapse by assaying serum samples for HCV RNA. Although eradication of the virus cannot be established, continued absence of relapse empirically indicates elimination of active infection, although residual HCV infection may be present.