Poly(D,L-lactide-co-glycolide) (PLG, 90:10) microspheres containing 20% norethisterone (NET) were prepared by solvent evaporation method. Microspheres in the size ranges of 65 to 100 microns were sterilized by irradiation and used for further study. In vitro release showed fairly constant release of NET from the above microspheres over more than 90 days. However, in vivo drug release determined by residual NET analysis after i.m. injection in rats indicated a faster release rate. About 95% of NET was released in a period of 45 days. At the dose of 80 mg of microspheres, vaginal estrus cycles were inhibited for 45 days compared to 27 days for the same dose of NET crystals in rats. Biodegradation of the microspheres was tested by direct measurement of molecular weight losses and SEM observation of morphological changes of the microspheres, which showed continuous erosion in the internal matrix of microspheres with the decrease of molecular weight of PLG until total collapse of microspheres, and biodegradation was faster in rats than in human serum at 37 degrees C in vitro. Total degradation of 90:10 PLG microspheres was less than 7 months in rats and more than 9 months in vitro.