Microspheres of blends of sodium alginate (NaAlg) and sodium carboxymethyl cellulose (NaCMC) were prepared by a water-in-oil (w/o) emulsion crosslinking method and used for the release of donepezil hydrochloride (DP), which is an Alzheimer's drug. The microspheres were characterized with Fourier transform infrared spectroscopy (FTIR), differantial scanning calorimetry (DSC), and scanning electron microscopy (SEM). The microsphere characteristics, including DP entrapment efficiency, particle size, equilibrium swelling degree (ESD), and DP release kinetics, were determined. The effects of the preparation conditions, including the NaAlg/NaCMC (w/w) ratio, drug/polymer (w/w) ratio, cross-linker concentration and time of exposure to the cross-linker, on the release of DP were investigated for successive gastrointestinal tract pH values of 1.2, 6.8, and 7.4 at 37 degrees C. The release of DP increased with the increase in NaAlg/NaCMC (w/w) ratio and drug/polymer (d/p) ratio, while it decreased with increasing extent of cross-linking. The optimum DP release was obtained as 99.13% for a NaAlg/NaCMC (w/w) ratio of 2/1, d/p ratio of 1/4, CaCl2 concentration of 5% and crosslinking time of 30min. It was also observed from release results that DP release from the microspheres through the external medium was higher at low pH (1.2) values than that at high pH (6.8 and 7.4) values. The DP release of the microspheres followed either Fickian transport below a value of n < 0.5 or anomalous transport (n = 0.5-1.0).