The purpose of this study was to develop an in situ forming SAIB (sucrose acetate isobutyrate)-PLGA (poly (d, lactide-co-glycolide)) mixture matrix depot for sustained release of risperidone. The factors affecting the risperidone release kinetics were investigated to obtain further insight into the drug release mechanisms. The burst release in vitro was significantly reduced (4.95%) by using DMSO as solvent. And, increasing the PLGA content from 2 to 10% w/w decreased the initial release from 6.95 to 1.05%. The initial release in vivo decreased with increasing PLGA content (2.0% w/w PLGA, C(max) = 1161.7 ± 550.2 ng ml(-1); 10% w/w PLGA, C(max) = 280.3 ± 98.5 ng ml(-1)). The persistence (AUC(4-20 days)) over 20 days increased from 76.8 ± 20.7 to 362.8 ± 75.0 ng d ml(-1) by inclusion of 10% PLGA compared with the PLGA-free depot. These results demonstrate that the SAIB-PLGA mixture matrix depot could be useful as a sustained delivery system for risperidone.