We have examined the effect of monomer structure on amine-anhydride reactions at a polymer-polymer interface. The thermodynamic interaction parameter χ was varied by changing the backbone chemical structure, holding molecular weight constant. To eliminate the effects of mixing, experiments were performed with bilayer thin films of end-functional polymers. Using a combination of size exclusion chromatography with fluorescent labeling, we measured the extent of reaction of anhydride-terminal poly(methyl methacrylate) and polystyrene with amine-functional polystyrene, polybutadiene, poly(ethylene/ethylethylene), and poly(dimethylsiloxane). Interfacial structure was observed by atomic force microscopy. Both the conversion to block copolymer and the degree of interfacial roughening are suppressed with increasing χ. This suppression may be related to reduced solubility of the reactive homopolymers in the formed block copolymer and to decreased interfacial volume for reactions to occur. Viscosity does not play a significant role in these studies. In melt blends of similar polymers prepared in a cup-and-rotor mixer, the rate of reaction and extent of conversion also generally decrease with increasing χ. The rates are up to 100 times faster, suggesting that convection sweeps away block copolymer that forms at the interface. These results indicate that thermodynamic interactions play a significant role in determining rates of reaction at polymer interfaces.