BACKGROUND AND AIMS: Retreatment with a combination of alpha interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies. METHODS: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000-1200 mg/daily depending on body weight) was given for 24-60 (mean 39.5) weeks. RESULTS: Biochemical end of treatment and sustained responses were observed in 271/581 (46.6\%; 95\% confidence interval (CI) 42.6-50.7\%) and in 109/581 (18.7\%; 95\% CI 15.6-22.0\%) cases, respectively. Two hundred and six of 532 patients (38.7\%; 95\% CI 34.6-42.9\%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7\%; 95\% CI 12.8-18.8\%). Fifty four of 581 patients (9.2\%; 95\% CI 7.0-11.7\%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment gamma-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008). CONCLUSIONS: The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal gamma-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30\%.