Bupivacaine-loaded comatrix, formed by bupivacaine-loaded microspheres included in a poly(lactide-co-glycolide) film, was assayed for the controlled release of the drug 'in vivo'. The comatrix, with 66.37 microg of bupivacaine, signifying a dose of 265.5 microg/kg, was subcutaneously implanted in the back of rats. Maximum plasma bupivacaine concentration was 147.6 +/- 5.0 ng/ml 95 h after the device implantation, and the drug was detected in plasma for 17 days. The half-life time of bupivacaine improves by more than 50 times with regard to that of the drug administered in a solution by intraperitoneal injection. After 15 days of implantation the comatrix was included in a thin fibrous capsule and degradation of the microspheres was observed. The histological studies show good biocompatibility of this comatrix. After 50 days the comatrix was degraded and its remains were almost indistinguishable from the surrounding tissue. Small number of microspheres was observed and they were surrounded by conjunctive tissue. Nerve packets and small blood vessels were also observed in the periphery of the implant.