Nitrendipine, a dihydropyridine calcium antagonist, was used as a poorly water-soluble model drug. To improve its dissolution rate and extend the therapeutic period in vivo as well, a novel pH-dependent gradient-release drug delivery system for nitrendipine having a solid dispersed matrix structure was developed. Four factors, i.e. the amount of excipients, the pH of the dissolution medium, the rotating speed of the paddle of the dissolution apparatus and the particle size of the microspheres, all of which affect the drug-release behavior of the pH-dependent microspheres of the system were investigated in detail. The release profiles of the pH-dependent drug delivery system under simulated gastrointestinal tract pH conditions were also investigated. The results showed that the release rate of drug from the microspheres increased on increasing the amount of respective pH-dependent polymers formulated. Due to the fact that the active drug was incorporated in pH-dependent polymers and was present in a solid dispersion state in the microspheres, the release rate of the drug from the microspheres depended on the dissolution rate of the polymers, which was mainly influenced by the pH of dissolution medium, whereas the rotating speed of the paddle and the particle size of the microspheres had only a relatively minor effect. The release behavior of the system under simulated gastrointestinal tract conditions exhibited obvious gradient-release characteristics, showing that the release rate of the active drug could be controlled efficiently before the microspheres reached the appropriate region of the gut for absorption. These findings suggest that the pH-dependent drug delivery system could be fabricated by using present microspheres.