Six treatment regimens using oxytetracycline (OTC) combined with streptomycin (ST) were evaluated for eliminating Brucella melitensis from 480 naturally-infected sheep and goats. Cessation of shedding Brucella from udder secretions and absence of Brucella in selected tissues at autopsy were considered criteria for successful treatment. Four regimens were equally effective in eliminating Brucella in the treated groups of sheep and goats regardless of the source of antibiotics used. These were regimen A (OTC 20 mg/kg intravenously daily for 6 weeks, combined with ST 20 mg/kg intramuscularly [i.m.] daily for 3 weeks), regimen B (long-acting [LA]-OTC 20 mg/kg i.m. every 3 days for 6 weeks, with ST 20 mg/kg i.m. every 3 days for 3 weeks), regimens D and E (LA-OTC 28 mg/kg i.m. every 3 days for 6 weeks, with ST 20 mg/kg i.m. every 3 days for 3 weeks). However, regimen C (LA-OTC 20 mg/kg i.m. every 3 days for 6 weeks, with ST 20 mg/kg i.m. every 3 days for 3 weeks) eliminated Brucella in only 75 of 80 (94%) sheep and goats. Regimen F (LA-OTC 25 mg/kg i.m. every 2 days for 4 weeks, combined with ST 20 mg/kg i.m. every 2 days for 2 weeks) was the most practical, effective and least expensive regimen for eliminating Brucella in the 80 treated sheep and goats. Brucella melitensis biovar 2 was repeatedly isolated from the mammary secretions of all sheep and goats before treatment. It was also isolated repeatedly from the udder secretions of all non-treated control animals and from selected tissue specimens collected from the controls at necropsy.