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The efficacy and toxicity of two regimens of antimony, 28 and 40 days of 20 mg of antimony/kg/day, were compared in the treatment of culture-positive mucosal leishmaniasis involving more than one anatomic site. Forty consecutive eligible Peruvians with infiltrative or ulcerative mucosal disease of the lips, nose, palate-uvula-pharynx, or larynx-epiglottis were randomized to receive either 28 days (P28) or 40 days (P40) of sodium stibogluconate (Pentostam). Treatment was prematurely terminated due to thrombocytopenia in three patients and two patients did not complete six months of follow-up. At one month post-treatment, 13% (2 of 16) of the P28 patients and 16% (3 of 19) of the P40 patients no longer had infiltrates or ulcers and were initially considered cured. During a further 11 months of follow-up, infiltrated lesions healed in eight more P28 patients and in 10 more P40 patients. The cure rate after 12 months of follow-up was therefore 63% for both groups (10 of 16 in the P28 group and 12 of 19 in the P40 group). The total of 13 patients who had infiltrates or ulcers at the 9–12-month follow-up were considered failures. All seven patients (three in the P28 group and four in the P40 group) whose lesions were culture-positive for Leishmania at some point in the 12 months after treatment, and who were thereby parasitologic failures, were also clinical failures. Since the cure rates did not differ between the two treatment regimens, there is no therapeutic advantage to increasing the length of treatment with Pentostam to 40 days in patients with mucosal leishmaniasis involving more than one anatomic site.