O. cynotis infestations were induced in barrier-reared mite-free cats. By monitoring the infested cats, sequence of humoral and cellular immune reactions to the mites was determined. Delayed hypersensitivity was not demonstrated in vivo, using intradermal skin tests. Reaginic (immunoglobulin E) antibodies, as detected by 72 h passive cutaneous anaphylactic reactions, were the earliest form of immune expression. Precipitating antibodies developed later in the course of the experimental infestation. Hematologic indices, including eosinophil counts, were not affected by established infestations. Antibodies prepared against feline whole blood, lymph, epithelium and RBC indicated that these regularly occurred in extracts prepared from whole mites. The feeding mode of mites required that they ingest feline tissue fluids. This mode is the interface by which the host becomes exposed to, and immunized against mite antigens.