Regional infusion chemotherapy delivers higher drug concentrations to the tumor than other methods and may decrease systemic drug levels. We evaluated the efficacy of degradable starch microspheres (DSMs) to further increase drug delivery to hepatic tumors. Rabbits implanted with hepatic Vx-2 tumors were treated with hepatic arterial infusion of doxorubicin hydrochloride labeled with carbon 14 with and without DSMs. Tissue levels of doxorubicin were measured in the heart, liver, and tumor 30 minutes after drug infusion. Blood drug levels, as well as biliary and renal excretion rates of doxorubicin, were determined. In rabbits receiving the drug alone, doxorubicin uptake by the tumor and liver were 17.1 +/- 12.8 and 55.3 +/- 9.5 nmol/g of wet weight tissue (mean +/- SD), respectively. In rabbits receiving doxorubicin mixed with DSMs, the tumor and hepatic drug levels were 59.7 +/- 24.9 and 50.7 +/- 4.8 nmol/g, respectively. The tumor drug level was significantly higher in the group that received DSMs compared with the group that received only the drug; the hepatic drug uptake was unchanged. Peak blood and cardiac drug levels were decreased by the coinfusion of drug and DSMs, suggesting that tumor response rates may be improved and systemic toxicity diminished by the use of DSMs in regional infusion chemotherapy.