The effects in vivo of the bisphosphonate drug pamidronate, used in bone resorption therapy, were investigated in an experimental model of cutaneous leishmaniasis. Pamidronate at an intraperitoneal dose of 10 mg/kg/day for 5 days effects a radical cure of cutaneous leishmaniasis in Balb/c mice, as evidenced by long-term disappearance of lesions; disappearance of amastigotes in lesion sites, as determined by histopathological analysis and cultivation of material obtained from lesions; and polymerase chain reaction analysis of necropsy material, using probes specific for kinetoplast DNA. Pamidronate is, therefore, a new lead compound for the synthesis of drugs effective against cutaneous leishmaniasis.