The method of application of the antibiotic tylosin (Tylan) for control of oxytetracycline-resistant American foulbrood (Paenibacillus larvae White) was tested in honeybee (Apis mellifera L.) colonies. A powdered sugar mixture with tylosin, applied as a dust, was efficacious in eliminating American foulbrood symptoms at a rate of 200-mg Tylan per 20 g of powdered sugar, applied at weekly intervals for 3 weeks. A second method of treatment consisting of Tylan mixed with granulated sugar and vegetable shortening and applied once as a patty, at an equivalent total dose as the dust method, to diseased colonies also effectively eliminated symptoms of disease. In all colonies treated with patties, however, small hive beetle (Aethina tumida Murray) populations significantly increased, compared with the powder sugar method or untreated controls. Bee populations in patty-treated colonies also were significantly reduced, most likely the result of the invasion and proliferation of adult and larval small hive beetles. Such reduction in colony strength was not seen in dust-treated colonies. Because of the obvious damaging populations of small hive beetles, concerns about development of disease resistance, unknown risks of residues, and lack of support by regulatory agencies for the use of the patty method, the use of the dust method of tylosin is greatly favored over the patty method.