Background/Aims: Interferon-α has been reported to acutely induce insulin resistance and glucose intolerance. The effects of long-term treatment with interferon-α on glucose metabolism remain unclear.Methods: Thirty-two Japanese patients with chronic hepatitis C were given interferon-α (6x10 6 U/day) daily for 2 weeks and thereafter 3 times weekly up to 6 months. The patients received a 75-g oral glucose tolerance test before the treatment. Fifteen patients also had an intravenous glucose tolerance test for an assessment of insulin sensitivity with Bergman's minimal model. These tests were repeated 3 months after the treatment.Results: Insulin sensitivity was not affected by the treatment (5.7+/-3.8 vs 5.2+/-3.8 10 - 4 .min - 1 .mU - 1 .l, not significant) and a statistically significant but minimum decrease in area under the curve of plasma glucose (1012+/-332 vs 928+/-282 mmol.1 - 1 .min, pvs 294+/-334 mU.l - 1 .min, pConclusion: Contrary to the known acute metabolic effects, interferon-α therapy for 3 months in patients with chronic hepatitis C did not have deleterious effects on insulin sensitivity and glucose tolerance.