Allopurinol is used for the therapy of canine leishmaniasis in Europe and it is currently the main treatment for this disease in Israel. Allopurinol treatment is oral, inexpensive and can be prescribed by the attending veterinarian and administered by the owners of the dog at home. This study was designed to assess the clinical and parasitological efficacy of allopurinol in dogs with visceral leishmaniasis (VL). Five dogs with naturally-occurring VL were treated with 20 mg/kg of allopurinol once daily for 8 months. The dogs were physically examined and tested pre- and during treatment. Testing included: the determination of serum anti-leishmanial antibody titers by ELISA, recording of globulin levels and albumin/globulin ratio, evaluation of the parasitological status by culture of splene and lymph node aspirates, xenodiagnosis and the determination of the infectivity to Lutzomyia longipalpis sand flies. RESULTS: Clinical improvement manifested by the return to physical activity, improvement of skin lesions and decrease in the size of peripheral lymph nodes were noted in all the dogs. Although the anti-leishmanial antibody titers decreased in the sera of all dogs, they remained seropositive. The drop in antibody titers was accompanied by the decrease in globulin levels and increase in the albumin/globulin ratio. Four of the 5 dogs remained parasitologically positive at the end of the study. Three dogs were tested by xenodiagnosis pre-treatment and four times during treatment. Initially these 3 dogs were infective to L. longipalpis with 89, 59 and 41 percent of the sand flies dissected positive for promastigotes, respectively. The % of infected sand flies decreased during the course of treatment and diminished by 4 to 5 months. The two additional dogs included in the study were parasitologically positive before the initiation of allopurinol treatment, and although they were not tested by xenodiagnosis pre-treatment, they too were not infectious to sand flies at the end of the study. In conclusion, daily allopurinol treatment of canine leishmaniasis at 20 mg/kgs can induce clinical improvement. Like other anti-leishmanial drugs used for treatment of canine leishmaniasis, it does not bring about parasitological cure in most cases. The sharp decrease in infectivity of treated dogs to L. longipalpis sand flies could be important in areas where disease transmission takes place.