Sustained release cephalexin microspheres have been formulated with poly(L-lactic acid) for intraperitoneal administration. Microspheres were prepared with spray-dried cephalexin by phase separation in organic solvent containing a fixed concentration of polymer, then sieve-sized. Batch-to-batch reproducibility of microsphere size distribution and encapsulation efficiency (>95%) were demonstrated. The quality of the microspheres was dependent on the rate of stirring during preparation and was highest as 400 rpm. Scanning electron micrographs revealed approximately spherical shapes and porous surfaces. The release of cephalexin followed second order dissolution model kinetics for multiparticulate systems. The apparent second order rate constant, k(2), was lowest for the highest sieve-size fraction (250-425 mu m) and varied with drug loading reaching a minimum at 33% w/w. A lower molecular weight PLA of 50 000 produced a faster release of cephalexin from microspheres. Cephalexin was released from microspheres for at least 4 h compared to only 10 min for complete dissolution of an equivalent weight of cephalexin powder, indicating sustained release which may be appropriate in treating localized infections.