The aim of the present study was to evaluate the long-term clinical outcome for dogs with leishmaniasis that were treated with 3 different protocols: combined treatment with antimony and allopurinol, antimony alone, or allopurinol alone. Ninety-six dogs included in this study were determined to have leishmaniasis on the basis of (1) clinical features, (2) identification of the parasite in smears of lymph node, bone marrow aspirates, or skin biopsies, and (3) specific immunofluorescent assay. Three groups of dogs were defined: 45 dogs (group 1) were treated with antimony (100 mg/kg s.c. q24h) given concurrently for 1 month with allopurinol (15 mg/kg p.o. q12h), and then allopurinol alone for 8 months at the same dosage; 40 dogs (group 2) were treated with antimony alone according to the manufacturer's instructions (200 mg/kg s.c. q24h at 2-day intervals for 3-6 months); and 11 dogs (group 3) were treated with allopurinol alone (15 mg/kg p.o. q12h for 1-20 months). Information concerning signalment, history, physical examination findings, serologic testing and number of dogs becoming seronegative, outcome for each treated dog (clinical cure versus failure), and long-term survival were recorded. The numbers of the clinical cures versus failures were significantly different among the 3 groups (chi2 = 17.77, P < .001), between groups 1 and 2 (chi2 = 8.02, P < .01), between groups 2 and 3 (chi2 = 11.00, P < .01), and between groups 1 and 3 (chi2 = 16.52, P < .001). No significant difference between groups 1 and 2 was noted in the type of failure (relapse or death), serologic test results, and number of survival years (chi2 = 2.79, P > .05). The results of the present study indicate that antimony in combination with allopurinol produces better results than antimony alone or allopurinol alone for the treatment of the canine leishmaniasis. With combination treatment, duration of treatment with antimony is shorter and long-term administration of allopurinol is well tolerated.