The ability of one stage of Rhipicephalus appendiculatus Neumann to induce resistance in a host to the feeding of the next stage in the life cycle was studied using Bos taurus cattle and rabbits. Simple resistance within a stage and cross-resistance between stages was generally less than 50%. The cumulative effect of simple resistance and cross-resistance over the whole life cycle in this experiment was estimated at 97% resistance measured as reduction in engorgement mass, numbers detached, and survival. Potential antigens in salivary glands of the three stages were compared by microscopy and electrophoresis and found closely similar. Production of serum antibodies against salivary antigens was examined by Western blotting of the electrophoretically separated salivary peptides. Cross reactions occurred but with little consistency. Hypersensitivity reactions were observed directly and tested immunologically. Only delayed hypersensitive reactions were directly involved in simple resistance and cross-resistance. These results can be applied in the selection of cattle for resistance to ticks, and this is discussed.