This work reports on the processes involved in the wear of hydroxyapatite sliding against slip-cast, glass-infiltrated alumina. Synthetic hydroxyapatite was used as a model material representing tooth enamel, while the alumina used was designed for tooth restorations. The wear tests were conducted in distilled water using a pin-on-disk tribometer under contact conditions that mimic the oral environment. To investigate the wear process for this material system, the surfaces of the hydroxyapatite “pin” and the alumina “disk” were examined by scanning electron microscopy and atomic force microscopy. Transmission electron microscopy was used to examine wear debris fragments collected from the hydroxyapatite wear scar and, for comparison, the bulk structure of the pin and crushed fragments from an unworn pin. Wear tracks on glass-infiltrated alumina showed only minor damage consisting of removal of glass from intergranular pockets in this material. In contrast, the hydroxyapatite wear surfaces were covered by an adhered debris layer, which obscured the rough, underlying surface. When dried, this adhered layer was found to contain both single-crystal and polycrystalline hydroxyapatite fragments, together with porous amorphous particulates, containing Ca, P, and O as major elements and Al and La as minor constituents. The composition of this amorphous wear product suggests a tribochemical reaction of hydroxyapatite and infiltrated alumina with water. The wear process, therefore, consists of material removal by fracture and deformation of the hydroxyapatite, followed by mixing of the crystalline fragments with the reaction products and the glass-infiltrate to form a uniform debris layer on the hydroxyapatite wear surface. The effects of this surface layer on wear are considered to include moderation of the local contact stresses and control of the immediate environment under which wear occurs. Our wear data, represented in terms of the wear factor, are found to be consistent with published data on the wear of tooth enamel sliding against different types of ceramic restorations.