This paper describes a matched case-control study to determine the efficacy of BCG vaccine in preventing the occurrence of leprosy in southern Malawi, a previously unstudied area. The BCG immunization rate amongst 145 individuals with leprosy was 44-8%, compared to 62-5% in 290 matched controls. The protective efficacy of BCG vaccine against leprosy in this region was estimated to be 63-6 %; smallpox immunization had no effect. These findings support the view that BCG vaccine should be considered as a control measure in areas where leprosy is endemic.