In chronic hepatitis C (HCV), standard interferon therapy with 3 MU three times weekly for 6 months is associated with sustained response in about 10-20% of patients while another 10-15% respond only when higher dosages or/and longer periods of treatment are used. Different variables have been described that are associated with sustained response and may also identify patients requiring low- or high-dose regimens. We have analysed a large data base of 442 patients with chronic hepatitis C treated with interferon-alpha to define rates of sustained response in different patient subgroups treated with different schedules. The rate of sustained response was increased with higher dose regimens in most patient categories, defined according to age, pre-treatment liver histology and HCV genotype, while the amount of interferon per one sustained response remained the same or was reduced. The use of higher dose regimen was particularly cost-effective in patients with cirrhosis. Using the same data base, different models of prediction of sustained response in the individual patient were developed and compared. Inclusion of the HCV genotype in these models was found to increase significantly specificity and sensitivity, confirming that this parameter has a major influence on sustained response to interferon therapy in chronic HCV.