Molecularly imprinted polymer nanoparticles were prepared in supercritical carbon dioxide using a noncovalent imprinting approach. In the present work, propranolol was used as a model template, methacrylic acid as a functional monomer, and divinylbenzene as a crosslinker. Under a high dilution condition, the heterogeneous polymerization resulted in discrete crosslinked polymer nanoparticles. Compared with the nonimprinted polymers, the imprinted nanoparticles displayed much higher propranolol uptake in a low polarity organic solvent. The use of a single enantiomer (S)-propranolol as the template clearly demonstrated that the imprinted binding sites are chiral-selective, with a cross-reactivity towards (R)-propranolol of less than 5%. The overall binding performance of the imprinted nanoparticles was comparable to imprinted polymers prepared in conventional organic solvents. (c) 2006 Wiley Periodicals, Inc.