Acrylic acid-esterified starch was produced by reacting starch with acrylic acid chloride. This reaction was rapid and easy to control. Introduction of acrylic groups into starch reduced the enzymatic degradability of starch (e.g., with 12 acrylic groups/100 glucose residues, approximately 75% of the degradation products eluted before glucose on gel filtration). The degradability could be increased to a large extent by preincubation at pH 5.5 in vitro (e.g., after 16 weeks, the corresponding figure was approximately 15%). The acrylic acid-esterified starch was used to prepare polyacryl starch microparticles. These were rapidly eliminated from the circulation after iv injection in mice, mainly by uptake in the liver. The elimination of the microparticles from the liver, monitored with [14C]starch, displayed a half-life of approximately 3.5-4.5 months. After 5 and 6 months, approximately 30% of the initial radioactivity remained in the liver. This is equivalent to the amount anticipated from the enzymatic degradation of the monomer (acrylic acid-esterified starch) in vitro and the innate nondegradability of the 14C-marker. These results, taken together, indicate that the ester bond between starch and the hydrocarbon chain in polyacryl starch microparticles is hydrolyzed at lysosomal pH.