Granulocytes and monocytes/macrophages (GM) are known to constitute extra-hepatic sites for hepatitis C virus (HCV) replication and dissemination. Accordingly, we thought that selective GM adsorptive apheresis (GMA) might contribute to the treatment of HCV in patients with high viremia (HCV-RNA > 100 kIU/mL). Of six patients (three males and three females), mean age 62.2 years, five had not responded to interferon-alpha (INF-alpha) and one was INF-alpha naïve. Each patient received five GMA sessions, once a week for 5 weeks. The two antecubital veins were used as blood access and return lines and the apheresis was performed at 30 mL/min for 60 min. Treatment efficacy was assessed by monitoring changes in plasma HCV-RNA and aminotransferase. Granulocyte and monocyte/macrophage adsorptive apheresis was well tolerated. During each GMA, there was on average a 52.9% fall in plasma HCV-RNA, but HCV-RNA increased again during the time before the next GMA. There was no marked change in either aminotransferase during GMA. Furthermore, beyond the last GMA, HCV-RNA increased together with worsening aminotransferase in three of six patients. In conclusion, it would appear that GMA can partially reduce plasma HCV and GMA at a frequency of one session/week for 5 consecutive weeks but that this was inadequate to induce a sustained decrease in plasma HCV-RNA in patients with high viremia without simultaneous administration of antiviral medications. The most effective frequency of GMA needs to be determined in future clinical studies.