Poly(D,L-lactide) microspheres loaded with cisplatin (PLA-CDDP MS) were prepared by a solvent evaporation technique for direct intratumoral injection. The microspheres, 50-100 microns, containing 40.04% of cisplatin produce sustained release in vitro. PLA-CDDP MS (6 mg/kg body weight of cisplatin) suspensions were injected intratumorally into mammary tumors in rats. Cisplatin solution (6 mg/kg body weight) was injected either intratumorally or intraperitoneally in two groups. After treatments, the tumor size decreased in each of the groups as a function of time. Sixteen days post-injection, the tumors had either disappeared or significantly shrunk. PLA-CDDP MS had a similar antitumor effect compared with cisplatin aqueous solution. Blood urea nitrogen, serum creatinine and histopathology examinations revealed that the renal toxicity in the PLA-CDDP MS group was significantly less than in the control groups. These results indicate that intratumoral injection of PLA-CDDP MS maintains anticancer potency and reduces acute renal toxicity.