The prophylactic efficacy of a long-acting oxytetracycline formulation was determined in 36 susceptible cows experimentally inoculated with Anaplasma marginale. Each of 10 cows in 3 treatment groups (T2, T3, T4) were given IM injections of 20 mg of oxytetracycline/kg of body weight once, twice, or three times during the prepatent period. The T2 group was treated once at 1 week after experimental inoculation, the T3 group was treated 2 times (at 1 and 2 weeks) after exposure, and the T4 group was treated 3 times (at 1, 2, and 3 weeks) after exposure. Six cows comprising group T1 served as nonmedicated controls. Treatment of cattle in the prepatent period with the long-acting oxytetracycline formulation produced significantly fewer clinical anaplasmosis cases. This reduction in frequency was proportional to the number of weekly treatments given. In cattle which developed clinical disease, only 1 IM injection of 20 mg of oxytetracycline/kg was necessary to induce recovery. The prepatent period in the treated cattle was extended approximately 30 days beyond the prepatent period of the control cattle after their final treatment. Humoral rapid card agglutinating and complement fixing antibodies regularly were present in the cows 10 days after they were inoculated; however, neither the presence of antibody nor that of the antibiotic was sufficient to prevent establishment of the carrier state in the principals.