Polylactide (PLA) microcapsules with an average diameter of 1.5μm were prepared by an interfacial deposition technique. The degree of degradation of PLA microcapsules was estimated by determination of the amount of lactic acid as a final product in bulk solution and from the molecular weight distribution of PLA of the microcapsules remaining undegraded by means of gel permeation chromatography using chloroform as the eluent. The rate of hydrolytic degradation of PLA microcapsules prepared by using poly (D, L-lactide) or poly (L-lactide) was extremely pH-dependent ; it was slowest at pH around 5.0 and it increased in both strongly acidic and strongly alkaline solutions. The activation energy of deesterification at pH 7.4 and ionic strength 0.15 was calculated to be 19.9kcal/mol for poly (D, L-lactide) microcapsules and 20.0 kcal/mol for poly (L-lactide) microcapsules, when the initial weight-average molecular weight was about 100000 for both polymers. These values are comparable to those found for the hydrolysis of alkyl acetates.¹⁾ In buffer solution (pH 9.6), the hydrolytic degradation was enhanced when the ionic strength of the medium was increased. Chromatographic analysis of the products of hydrolytic degradation suggested that OH^- or H₃O⁺ attacks the ester bonds located in the crystalline zone, followed by further cleavage of the initial products into fractions with lower molecular weights. Carboxylic esterase promoted the degradation by cleaving the ester bonds located in the crystalline zone directly. Urea and NaSCN accelerated the degradation effectively, while AlCl₃, CaCl₂, and KCl had no or little effect on the degradation rate. Poly (L-lactide) microcapsules were degraded less rapidly than poly (D, L-lactide) microcapsules.