A model was developed for interdiffusion at interfaces of polymers with dissimilar physical properties. This model is based on the assumption that the monomeric friction coefficients of the two polymers are identical but a strong function of the matrix composition. The composition dependence of the monomeric friction coefficient was evaluated from the blend zero-shear viscosity using the reptation theory. In turn, the compositional dependence of the blend zero-shear viscosity was evaluated using the volumetric properties of the blend and the free-volume theory. For polymers with dissimilar properties, this model predicts that the concentration profiles are highly asymmetric, with substantial swelling of the slower-diffusing component by the faster-diffusing component. This model also predicts the effect of changes in the volume of mixing on interdiffusion at polymer/polymer interfaces. The model was applied to a polymer pair with very dissimilar physical properties consisting of polystyrene and poly(vinyl methyl ether) and to a polymer pair with relatively similar properties consisting of poly(vinyl chloride) and poly(methyl methacrylate), to predict the concentration profile.