The objective of present investigation was to evaluate the entrapment efficiency of the anti-HIV drug, zidovudine, using two Eudragit polymers of different permeability characteristics and to study the effect of this entrapment on the drug release properties. In order to increase the entrapment efficiency optimum concentration of polymer solutions were prepared in acetone using magnesium stearate as droplet stabilizer. The morphology of the microspheres was evaluated using a scanning electron microscope, which showed a spherical shape with smooth surface. The mean sphere diameter was between 1000-3000 microm and the entrapment efficiencies ranged from 56.4-87.1%. Polymers were used separately and in combination to prepare different microspheres. The prepared microspheres were studied for drug release behavior in phosphate buffer at pH 7.4, because the Eudragit polymers are independent of the pH of the dissolution medium. The release profiles and entrapment efficiencies depended strongly on the structure of the polymers used as wall materials. The release rate of zidovudine from Eudragit RS 100 microspheres was much lower than that from Eudragit RL 100 microspheres. Evaluation of release data reveals that release of zidovudine from Eudragit RL 100 microspheres followed the Higuchi rule, whereas Eudragit RS 100 microspheres exhibited an initial burst release, a lag period for entry of surrounding dissolution medium into polymer matrix and finally, diffusion of drug through the wall material.