This article presents a unique example dealing with how chemical reactions between immiscible polymers in the melt behave differently than they would do in solution. Specifically, a model reaction was chosen : the transesterification between poly(ethylene-co-methyl acrylate) (EMA) and polystyrene mono-hydroxylated at the chain end (PSOH). It was carried out in the melt in a batch mixer. The overall rate of this reaction has a similar dependence of temperature, composition of reactants, and the nature and concentration of catalyst as in solution. The reactivity of PSOH decreases drastically with increasing molecular weight, and it becomes very weak when the molecular weight exceeds 8000 g/mol. As opposed to a reaction in solution or in a homogeneous melt, mechanical mixing increases the reaction rate since it generates interfacial area and reduces the diffusion length. The EMA-g-PS graft copolymer formed at the interfaces reduces the interfacial tension, and increases the miscibility of the reaction mixture. However, its occupation of the interfaces reduces contact between the reactive moieties, thus decreasing the overall reactivity. More importantly and much to our surprise, adding 1 to 2 wt% of an inert solvent increased greatly the overall reaction rate. While an increased interfacial mixing and diffusion by the presence of minor amounts of solvent are though to be the major factors contributing to the drastic increase in reactivity, numerous questions still remain. Nevertheless, this study clearly showed that as opposed to a reaction in solution, mechanical mixing and the presence of minor amounts of solvent are two additional and critical means to control chemical reactions between immiscible polymer melts.