An intra-articular polymeric controlled release system was developed that is tailored to, and responsive to, the intensity of joint inflammation. Microspheres composed of the naturally occurring polyelectrolytes, gelatin and chondroitin sulfate, were synthesized by complex coacervation and the kinetics of release of encapsulated 14C-catalase was evaluated in vitro in the presence of inflammatory and non-inflammatory human joint fluids. The relative activity of gelatinase, a metalloprotease enzyme, was quantified in each of the joint fluids. Rate of degradation of the microspheres, and consequent release of 14C-catalase, was found to parallel the relative gelatinase activities in the joint fluids. Furthermore, various methods of crosslinking were found to affect the kinetics of microsphere degradation in the fluids. A catalase loading level of up to 28% was achieved, and the encapsulated catalase was found to retain up to 58 % of its biological activity.