Twenty-four Collies sensitive to the toxic effects of ivermectin, when administered at high dosages, were studied to evaluate the effects of repeated monthly treatment with an ivermectin beef-based formulation at amounts up to 10 times the dosage recommended for heartworm prevention in dogs. Collies were treated 3 times at 30-day intervals at rates of 12, 36, or 60 micrograms of ivermectin/kg of body weight, or with vehicle. Complete physical and neurologic examinations were performed on all dogs prior to the first treatment and after the final treatment. Clinical observations and ivermectin reaction scores were recorded daily for each dog throughout the study. Clinical or neurologic signs characteristic of ivermectin toxicosis were not observed for any dog during the study. Single episodes of vomiting were recorded for 2 vehicle-treated dogs and 2 dogs treated with ivermectin at 12 micrograms/kg from 6 to 21 days after treatment. At the end of the study, all dogs were challenge-exposed with ivermectin at 120 micrograms/kg to reconfirm their sensitivity to this class of compounds. All dogs developed signs typical of ivermectin toxicosis during the subsequent 48- to 72-hour period. Results of this study demonstrated that ivermectin can be administered repeatedly without adverse effects at rates up to 60 micrograms/kg (10 times the recommended use level) to Collies known to be sensitive to this drug.