A model drug with limited water-solubility, chlorothiazide, was successfully encapsulated in whey protein-based wall systems cross-linked by glutaraldehyde-saturated toluene via an organic phase. The effects of drug content of the core-in-wall suspension and of cross-linking conditions on core retention and on microcapsule size, structure and core release properties were investigated. Spherical, surface cracks-free microcapsules ranging in diameter from similar to200-1300 mum were obtained. Particle size distribution of microcapsules was affected by core content and cross-linking conditions. Core retention in microcapsules prepared at different cross-linking conditions and different wall-to-core ratios ranged from 48.9-81%, from 42.2-76.1% and from 37.3-67.2% in large (L), medium-size (M) and small (S) microcapsules, respectively. In all cases, drug crystals were physically entrapped and embedded throughout the cross-linked protein matrix. Core release from the microcapsules into enzyme-free simulated gastric fluid was governed by a diffusion-controlled mechanism and did not involve erosion or softening of the wall matrix. Rate of core release was significantly affected by a combined influence of core content, microcapsule size and cross-linking density. Complete core release from L, M and S microcapsule prepared at different wall-to-core ratios and cross-linking conditions ranged from 28.6-81.2 h, from 16.8-28.6 h and from 7.2-15.9 h, respectively. Results suggested that whey protein-based wall matrix cross-linked by GAST may provide significant opportunities in modulating the release of an encapsulated core with a limited water solubility.