The authors present a case of acute renal failure, acute hemolysis and thrombocytopenia due to intermittent use of Rifampin for leprosy. These adverse reactions have rarely been discribed in the medical literature. During follow up there was recovery of renal function and complete remission of the hematological alterations. To our knowledge, this has been the first report of such adverse effects of Rifampin during leprosy therapy in Brazil. Pathogenetic aspects are discussed and current literature is reviewed.