Objective: To identify the interferon-alpha (IFN alpha) treatment protocol most suitable for patients with thalassaemia major who have chronic hepatitis C. Design and setting: This was a meta-analysis of studies in the international literature between 1990 and 1999. Methods: Studies were identified from a search of Medline and Embase, and analysed by the Mantel-Haenszel-Peto statistical method. Results: We identified 6 nonrandomised trials, 2 of which were controlled, that treated a total of 201 patients, Most studies used the lowest dose level (3 MIU/m(2)), all used a thrice-weekly regimen, and most used IFN alpha-2b, although the use of natural IFN alpha did not induce production of anti-interferon antibodies. The best sustained response and remission rates tended to be achieved with higher doses and longer cycles of IFN alpha. Conclusions: The best interferon-based therapy to treat polytransfused thalassaemic patients with chronic hepatitis C is represented by the use of natural IFN alpha or IFN alpha-2b, initially at high dosages (5 to 10 MIU/m(2) 3 times weekly) for 6 months, followed by lower dosages (3 MIU/m(2) 3 times weekly) for a further 6 to 9 months.