A retrospective study was performed on 27 patients withhepatitis C (HCV)-rela ted mixed cryoglobulinemia (purpura,arthralgia, hepatitis, glomerulonephritis, p eripheral neuropathy)to assess peripheral nerve involvement during follow-up of up to 8 years. All patients had the same degree of organ/system involvement ini tially and were clinically evaluated at least annually. All 27 patients received steroids; 15 also received recombinant interferon-α2b (rIFN-α2b). At first examination, neurological signs and electrodiagnostic findings consistent with p eripheral neuropathy were found in 20(74%) and in 24 (88.8%) patients, respect ively. Neurological evaluation and electrodiagnostic data at 3 and 8 years revea led worsening of neuropathy, whereas the other manifestations of mixed cryoglobu linemia (MC) were stable. At the last examination, clinical and electrodiagnosti c signs of neuropathy were found in 25 patients (92.5%), occurring in 1 of 3 pa tients with normal initial findings, and worsened in 8. A more severe neuropathy was observed in 3(25%) of the patients treated with prednisone alone and in 6 (40%) of the patients additionally treated with rIFN-α2b.Our data confirm tha t in patients with HCV-related MC, peripheral nerve involvement is frequent, is progressive, and does not seem to benefit by addition of rIFN-α2b to steroid treatment. A retrospective study was performed on 27 patients with hepatitis C (HCV) -rela ted mixed cryoglobulinemia (purpura, arthralgia, hepatitis, glomerulonephritis, p eripheral neuropathy) to assess peripheral nerve involvement during follow-up of up to 8 years. All patients had the the same degree of organ / system involvement iniially and were clinically evaluated at least annually. All 27 patients received steroids; 15 also received recombinant interferon-α2b (rIFN-α2b). At first examination, neurological signs and electrodiagnostic findings consistent with p eripheral neuropathy Neurological evaluation and electrodiagnostic data at 3 and 8 years revea led worsening of neuropathy, while the other manifestations of mixed cryoglobu linemia (MC) were stable. At the last examination, clinical and electrodiagnosti c signs of neuropathy were found in 25 patients (92.5%), occurring in 1 of 3 pa tients with normal initial findings, and worsened in 8. A more severe neuropathy was observed in 3 (25%) of the patients treated with prednisone alone and in 6 (40%) of the patients treated with rIFN-α2b. Our data confirm tha t in patients with HCV- related MC, peripheral nerve involvement is frequent, is progressive, and does not seem to benefit by addition of rIFN-α2b to steroid treatment.