We assessed the efficacy of rifampicin in the treatment of cutaneous leishmaniasis (oriental sore) using a double-blind placebo-controlled study. We studied 46 patients with cutaneous leishmaniasis, of whom 23 received rifampicin (group A) and another 23 received placebo (group B) for a period of 4 weeks. Each patient was assessed clinically for size of lesion, type of lesion, duration of lesion, number of lesions, and distribution of lesions, initially, and at the end of 1 week, 2 weeks and 4 weeks. Biochemical tests including enzyme studies were done to detect any toxic effects of the drug. Group A patients received rifampicin 1200 mg/day in two divided doses and group B patients received two doses of an identical placebo capsule. Seventeen (73.9%) of the 23 patients receiving rifampicin had complete healing. Two (8.6%) had partial healing and four (17.3%) showed no response, whereas out of 23 patients receiving placebo one patient (4.3%) showed complete healing, eight (34.7%) patients showed partial healing and 14 (60. 98%) patients showed no healing or exacerbation of lesion. The difference was statistically significant in favour of response to rifampicin. This dose of rifampicin was well-tolerated and no side-effects were seen in any patient. In cases of cutaneous leishmaniasis where injectable treatment is not feasible or not acceptable, as in cases of multiple lesions, rifampicin is a better alternative oral treatment. It is simple to administer, cheap, more effective and less toxic than other available oral drugs, and well-tolerated by patients.