The objective of the present investigation was to improve the efficiency of encapsulation of zidovudine (AZT) in poly(lactide/gycolide) (PLGA 50:50) by modifying the secondary aqueous phase. Surface morphology of the microcapsules was unchanged during the partial saturation of the aqueous phase with calcium chloride. However, partial saturation of the aqueous phase with AZT and a change in the pH of the aqueous phase showed significant effect on the surface morphology. The surface appeared to be wrinkled when the pH of the aqueous phase was adjusted to 10. The particle size was between 8 and 18 μm. The particle size was increased significantly (78-140 μm) when the aqueous phase was partially saturated with AZT (0.25-0.75%). The efficiency of encapsulation did not change when the aqueous phase was partially saturated with calcium chloride (5-30%). The efficiency of encapsulation was pH dependent. The encapsulation increased up to 17% when the aqueous phase was partially saturated with 0.75% AZT. The cumulative drug release from the microcapsules was between 15 and 34% within the first 24 h. A sustained drug release continued up to 60 days.