Reported in this paper is the preparation of fluorescent nanospheres from poly(solketal acrylate)-block-poly(2-hydroxyethyl acrylate) or PSA-PHEA. The strategy involved the chemical derivation of the PHEA block to graft the fluorophore fluorosceinamine (Fl) first. A selective solvent for PSA was then used to induce micelle formation from the diblock with PSA as the corona and the fluorescein-tagged PHEA block as the core. Nanospheres with fluorescent cores were obtained after PHEA core crosslinking with succinyl chloride. Water-dispersible nanospheres were prepared after removing the acetonide groups from the PSA block by hydrolysis to yield poly(glyceryl acrylate). Such nanospheres may find applications in fluorescent in situ hybridization assays. (C) 2004 Elsevier Ltd. All rights reserved.