The objective of present study was to control the delivery of leuprolide acetate using in situ forming microparticle (ISM) systems. A solution of leuprolide acetate and poly(lactide-co-glycolide) (PLGA RG 503H) or poly(lactide) (PLA R 202H) in N-methyl-2-pyrrolideone (NMP) was emulsified into an external oil phase using a two-syringe/connector system. After injection into an aqueous environment, NMP diffusion led to polymer precipitation and microparticle formation in situ. ISM-systems were characterized with respect to particle morphology and the influence of formulation and processing parameters on the in vitro release. ISM from RG 503H showed a high initial release (approximately 40%), which could be attributed to the high porosity of microparticles. The initial release could be reduced by increasing the polymer concentration, increasing the amount and viscosity of the oil phase, and decreasing the drug loading. ISM-systems from R 202H had a much lower initial release (approximately 9%) compared to that from RG 503H, which was followed by a slow and continuous drug release. In comparison to conventional microparticles prepared by a solvent evaporation method, ISM from R 202H showed a lower initial release and a more linear continuous release.