This work aims to clarify the effect of nanoparticle self-agglomeration structure on the morphology of polymer blends. The morphology development of polystyrene (PS)/polyamide (PA6) blends with titanium dioxide (TiO2) nanoparticles preferentially localized in the PA6 domains was investigated by means of electron microscopy observation, viscoelastic analysis and selective extraction tests. It was shown that the preferential dispersion of TiO2 leads to a significant reduction of the PA6 continuity in the PS/PA6 blend. The size of the PA6 domain increases gradually with further increasing the nanoparticle loading whereas the co-continuity of the PS/PA6/TiO2 mixture is destroyed by isothermal post-treatments. These experimental results are completely different from those in carbon black, nanoclay or nano-silica-filled immiscible polymer blends. To elucidate the progression to the uneven morphology change, the dynamic process of microfibril break-up and droplet coalescence in the molten PS/PA6/TiO2 mixture was traced in real-time through optical microscopy. It was confirmed that the self-agglomerating pattern of the nanoparticle in the polymer melts plays a key role in directing the morphology evolution of the immiscible polymer blend: unlike the self-agglomeration of carbon black to form three-dimensionally continuous network structure, the TiO2 nanoparticles tend to form separate clusters in the PA6 phase. This prevents PA6 droplets from fusing together to form a continuous network during the coalescence and producing larger PA6 domains at higher TiO2 loads. (C) 2011 Elsevier Ltd. All rights reserved.