Polymerization of diethyl methylidenemalonate (DEMM, 1a) in 0.1 M phosphate buffer containing 1% dextran 70 yields nanoparticles of a diameter ranging from 140 to 250 nm depending on the pH value (6.7 to 8.7). The weight-average and number-average molecular weight of the resulting polymer were 3791 and 1084, respectively. Approximately 95% of the 14C-labeled poly(DEMM) nanoparticles were found in liver and spleen 1 h after iv administration. A statistically significant (p less than 0.01) approximately 10% decrease of the radioactivity was observed in the liver over a 3-month period. The poly(DEMM) nanoparticles were not absorbed and were totally cleared from the gastrointestinal tract 24 h after oral dosage. The very slow bioelimination process observed after iv administration limits the usefulness of poly(DEMM) nanoparticles as a systemic drug carrier. Nevertheless, their oral administration as bioavailability enhancers can be envisaged. Moreover, the fact that nanoparticles are readily produced in a medium near neutrality should be emphasized.