The effect of pH and drug solubility on the release kinetics of sodium alginate matrices has been studied. Release of a highly soluble model drug, chlorpheniramine maleate, was significantly faster in simulated gastric fluid (SGF) than in simulated intestinal fluid (SIF), whereas the opposite effect was observed for hydrochlorothiazide, a drug of poor solubility. These results could be explained in terms of the internal microscopic structure of the hydrated surface layer formed on matrix hydration and by the different hydration kinetics of the polymer in these two media. Cryogenic electron microscopy revealed the hydrated surface layer formed by alginate matrices in SGF to be particulate and porous in nature, in contrast to the highly hydrated continuous gel layer formed in SIF. Drug release mechanisms were discussed with respect to drug solubility and the structure and properties of the surface layers formed by alginate matrices when hydrated in different pH media.