The solid state reaction between metalorganic chemical vapor deposition grown epitaxial ZnO films and the R-plane sapphire substrate after annealing at 1000 °C for various times in an O2/N2 atmosphere was studied in detail. Multiple epitaxial relationships between the reaction product (ZnAl2O4) and the reactants were observed, as determined by cross-sectional transmission electron microscopy. In the dominant epitaxial relationship (A1), the (22¯0) plane of ZnAl2O4 was parallel to the (1¯101) plane of Al2O3. A twin (A2) of orientation A1, i.e. (22¯0) ZnAl2O4//(101¯1) Al2O3, and a closely related orientation (B) wherein the (22¯0) ZnAl2O4 plane is parallel to the (1¯21¯0) ZnO plane (which is equivalent to a 5° clockwise rotation about the [1¯1¯2] ZnAl2O4 or  ZnO zone axis relative to A2), were also obse- rved. Enhanced growth was observed at grain boundaries. It was necessary to measure the spinel growth rate from grains with the same orientation far away from grain boundaries because the growth rate was observed to be influenced by the orientation of the grains in addition to the enhanced growth at grain boundaries. The growth rate was observed to follow a linear rate law during early stages (for grains with orientation A1), suggesting an interface-controlled reaction. The structures of the ZnO/Al2O3, ZnO/ZnAl2O4 and ZnAl2O4/Al2O3 interfaces were studied for grains with this orientation (A1). The 13.7% lattice mismatch between ZnO and ZnAl2O4 was relieved by a series of misfit dislocations spaced five to six (11¯00) ZnO planes apart. Due to the small lattice misfit (2.1%) at the ZnAl2O4/Al2O3 interface, very few misfit dislocations were present. This interface was faceted and the sapphire surface had a series of single steps. It is expected that the reaction at the ZnAl2O4/ZnO interface is the rate-controlling step due to the necessity for a dislocation climb (of a large number of misfit dislocations) for movement of this interface.