Background/Aims: Chronic viral hepatitis is associated with elevated serum iron indexes, and iron accumulation in the liver may contribute to liver injury and fibrosis due to hepatitis as well as increased risk of developing hepatocellular carcinoma. We studied the effect of iron depletion on the response to subsequent interferon therapy in chronic hepatitis C. Methodology: A population of 83 patients affected by chronic hepatitis C who had not previously under gone any specific therapy and who had laboratory confirmation. of iron overload (serum, ferritin >400ng/mL in the, males and >300ng/mL in the females) was divided into two homogeneous' groups. The 43 patients in Group A underwent phlebotomy (300mL every 10-15 days for an average total of 8 sessions) until their serum ferritin levels were < 100ng/mL, The 40 patients in Group B were treated with interferon without prior iron depletion. Results: In Group A, iron depletion alone induced a highly significant (p<0.01) reduction of alanine aminotransferase serum values: from 165 U/L (range: 60-370 U/L). Seventy-six patients completed therapy and follow-up: a complete and sustained response was obtained in 12/39 cases in Group A and in 6/37 cases in group B (p<0.05). Conclusions: Iron deletion carried out in, patients,p with chronic hepatitis C who have elevated serum ferritin values induces a significant reduction in necro-inflammatory activity (notable decrease in average alanine, aminotransferase values) and improves their response to subsequent treatment with interferon, although it does not modify the viral load.