This paper deals with the study of new interfacial instabilities, called grainy defects, in coextrusion process of reactive multilayer polymers. The main objective was to better understand this phenomenon since no help can be found in the literature. The fundamental approach from a micro-scale to a macro-scale involves the study of relationships between polymer structure, processing, and interfacial properties. The influence of these parameters on the generation of grainy defects during coextrusion has been assessed in correlation with physicochemical properties. Through this work, rheological properties and the interfacial morphology between tie and barrier layers have been investigated by shear stress relaxation experiments and transmission electronic microscopy, respectively. Depending on the reactive polymers, the interfacial coupling was found to significantly alter the stress relaxation behavior by extending the relaxation time and generating an interfacial roughness. Hence, relations between the copolymer architecture, the relaxation process, and the interfacial morphology were established in correlation with the generation of grainy defects in coextrusion process. POLYM. ENG. SCI., 55:2542-2552, 2015. (c) 2015 Society of Plastics Engineers