Leprosy type 1 reactions (T1R) are immune-mediated events with inflammation of peripheral nerves and skin. We report the clinical outcomes of a closely monitored open prospective trial in which eight Nepali and 33 Ethiopian patients with T1Rs were treated with an Indian generic formulation of ciclosporin (Cn; 5-7.5 mg/kg/day) for 12 weeks and followed up for 24 weeks after starting treatment. Outcomes were measured using a clinical severity score. Among the Nepalis, 75-100% improved in all acute clinical parameters; 67-100% patients maintained improvement, except for those with acute sensory nerve impairment among whom 67% relapsed after stopping treatment. The skin lesions of all Ethiopians on 5 mg/kg/day of Cn improved and 50-60% had peripheral nerve function improvement. Most Ethiopians needed a higher dose of Cn to improve nerve impairment and neuritis, and 50-78% of them developed worse clinical severity scores when Cn was stopped. Four Ethiopians and two Nepalis developed elevated serum creatinine levels on 7.5 mg/kg/day Cn, and three (9%) Ethiopians developed treatable hypertension. This suggests that Cn monotherapy is an effective treatment for severe T1R with few adverse effects. A dose of 5 mg/kg/day seems efficacious in Nepalis, but a higher dose may be required in Ethiopian patients.