A double-blind, internally-controlled, clinical trial of thalidpmide in severe, chronic, histologically-proven erythema nodosum leprosum (ENL) is reported. A total of 10 adult male patients were admitted to the trial, all of whom were receiving continuous treatment with steroids and whose minimum daily requirement just to suppress the reaction was in no case less than 15 mg of prednisolone or 18 international units of corticotrophin. The trial wa s divided into 4 equal parts (of either 4 or 6 weeks' duration) consisting of an initial control period, first and second trial periods, and a final control period. Throughout the trial all patients received DDS, 100 mg twice weekly ; thalidomide, 300 mg daily, wa s given during one trial period and identical placebo tablets during the other. As judged by the red uction in their steroid requirements, 9 of the 10 patients showed a very significant improvement while they were receiving thalidomide, although 7 subsequently relapsed after stopping the drug. There was no dose-for-dose relationship between thalidomide and prednisolone. Two patients developed a mild allergic dermatitis.