In this study, we tested the hypothesis that outer membrane immunization would induce protection against an antigenically variant strain. Outer membranes were isolated from the Virginia strain of Anaplasma marginale using density gradient centrifugation, combined with saponin adjuvant, and used to immunize Friesian cattle in Zimbabwe. Immunized cattle developed high antibody titers (80,000-160,000) against outer membrane polypeptides including MSP-2 and MSP-5 in both the homologous Virginia and heterologous Zimbabwe strains. Outer membrane immunized cattle were protected significantly following challenge with 10(4) Zimbabwe strain parasitized erythrocytes, demonstrated by significant differences in prepatent period and peak rickettsemia compared with adjuvant immunized control cattle. One outer membrane immunized animal was completely protected against infection. However, there were no overall significant differences in severity of anemia between cattle immunized with outer membrane and the control group, indicating that a significant reduction in rickettsemia does not necessarily result in less severe anemia.