In a nonblinded, therapeutic trial conducted in Colombia, 1.25-1.5 grams of mefloquine base given as a single oral dose or as 250 mg a day for 5-6 consecutive days was not efficacious in the treatment of New World cutaneous leishmaniasis. The drug had cured only 30.8 % of patients with leishmaniasis skin lesions by the 10th week after start of therapy as compared with a 27.9% complete cicatrization rate in historical controls treated with placebo tablets and an 86.3% cicatrization rate in historical controls who received meglumine antimoniate, 20 mg/ kg/day intramuscularly for 20 days, with no upper limit to daily dose. It is concluded that a single course treatment with mefloquine is not indicated as monotherapy in the treatment of Colombian cutaneous leishmaniasis primarily due to L. panamensis.