Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE. Patients and Methods: We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE. Results: Without PE, IFN C<sub>max </sub>(range: 100–750 IU/ml) was obtained 3–6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-α area under the curve decreased from 3,005 IU·h/ml (1,563–4,614) on days without PE to 2,142 IU·h/ml (973–4,123) on day with PE. Conclusions: In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-α and PE therapy schedule have to be further studied to optimize its biological activity.