Abstract.To evaluate the effective role of hepatitis viruses in thalassemic (Th) liver disease, we carried out a long‐term study in 42 subjects with nontransfusion‐dependent Th minor hospitalized for an episode of acute viral hepatitis. 10 patients had serologic evidence of hepatitis A, 23 of hepatitis B and 9 of hepatitis non‐A, non‐B. In the follow‐up chronic hepatitis was detected histologically in 5/23 patients with hepatitis B and 5/9 with hepatitis non‐A, non‐B. All hepatitis A patients recovered completely. The prevalence in 7 out of 10 patients with chronic hepatitis of piecemeal necrosis and of inflammatory changes over hepatic siderosis and fibrosis evidenced a determinant role of chronic viral infection in the development of liver damage in these patients. Thus, heterozygous nontransfusion‐dependent Th patients seem to have a high risk of developing a chronic inflammatory liver disease especially after an episode of non‐A, non‐B hepatitis. Therefore, in our geographical area, chronic hepatitis of viral origin should be taken into account, among other pathogenetic factors, in many cases of cryptogenic thalas