Thirty cows naturally infected with Brucella abortus were treated by various routes, using free or liposomal streptomycin or a combination of liposomal streptomycin and a long-acting oxytetracycline preparation. Of 21 cows treated with liposomal streptomycin alone, 3 (14%) were culture negative and 3 had 10 or fewer bacterial colonies isolated from tissues obtained at necropsy. Thirteen (62%) cows continued to shed organisms in udder secretions and were considered treatment failures. Of 9 cows that were given a combination of liposomal streptomycin and long-acting oxytetracycline, 5 (56%) were cured, 3 had 10 or fewer colonies on culture plates of tissue after necropsy and only 1 continued to shed B abortus in udder secretions after treatment. Eleven cows were given streptomycin liposomes by intramammary infusion with or without IM administration of long-acting oxytetracycline. The most effective regimen consisted of 2 intramammary infusions of streptomycin liposomes and 2 doses of oxytetracycline administered IM. Of 5 cows treated thusly, 2 were cured and all others had fewer than 10 B abortus colonies isolated from tissues obtained at necropsy.