Positron annihilation lifetime spectroscopy (PALS) and differential scanning calorimetry (DSC) were used to study the interdiffusion in a particle matrix system consisting of (styrene-maleic anhydride) copolymer containing 24% maleic anhydride (SMA) and poly(methyl methacrylate) (50:50). Starting from the phase separated state of the miscible components, the transition to the mixed state due to interdiffusion during annealing at 160 and 180 degreesC was investigated. The diffused mass fractions of both components were estimated by DSC; they increase linearly with the logarithm of the annealing time. Both components show the same behavior, suggesting an average interphase composition of 50:50. For subsequent annealing, the kinetic behavior differs from the earlier behavior, probably because of the different diffusion coefficients of the two components. Experimental evidence is presented that the ortho-positronium (o-Ps) intensity correlates to the interdiffusion process. The response is due to the diffusion of inhibitors for Ps formation from one phase into the other. A semi-quantitative model is developed that allows the estimation of the interphase volume fraction from the relative change of the annihilation parameters. The PALS results are discussed in relation to those obtained by DSC. The results show that PALS is a useful tool to study mixing and demixing processes in polymer blends with a three-dimensional morphology.