Hemoparasitic diseases are endemic in half the world's livestock production areas and are the greatest obstacle to improved meat, milk, and fiber production in the Third World. The most prevalent of these diseases, anaplasmosis, occurs throughout tropical and subtropical regions and is responsible for 50,000 to 100,000 cattle deaths annually in the United States alone. Despite its prevalence and the severity of the losses, an effective immunoprophylaxis for anaplasmosis has not been developed. A neutralization-sensitive epitope on a surface protein with a molecular weight of 105,000 (Am 105) of the causative rickettsia Anaplasma marginale was identified by monoclonal antibody inhibition of infectivity. This epitope was determined to be common to eight isolates with antigenic, morphologic, and protein structural differences. Cattle immunized with Am 105 purified by immunoaffinity chromatography were protected against challenge with virulent Anaplasma marginale. The identification of Am 105 as bearing isolate-common epitopes capable of inducing protection in immunized cattle provides the basis for the development of an effective subunit vaccine for bovine anaplasmosis.