We have fabricated unilamellar lipid bilayer VESicle-COated hydrogel spheres (VESCOgels) by carbodiimide-mediated coupling of liposomes bearing surface amines to core shell hydrogel spheres bearing surface carboxyls. The amine-containing moiety, 3-O (2-aminoethoxyethyloxyethyl)carbamyl cholesterol (AECHO), was incorporated into large unilamellar vesicles (LUVs), diameter similar to 100 nm, composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The hydrogel, diameter similar to 1 mu m, consisted of a core of poly(N-isopropyl acrylamide) (pNIPAM) and a shell of p(NIPAM-co-acrylic acid (AA)). Activation of these surface-displayed carboxyls with N-hydroxysuccinimidyl (NHS) esters permitted amine coupling upon addition of AECHO-containing POPC LUVs. Bilayer integrity of the hydrogel-bound LUVs was maintained, and fusion of LUVs did not occur. Fluorescence assays of the release of cobalt-calcein trapped within hydrogel-bound LUVs and of sodium fluorescein trapped within the hydrogel itself showed that each compartment retained its distinct release attributes: fast release from the microgel and slow release from the LUVs. It is envisioned that VESCOgels will be useful, therefore, in applications requiring temporally controlled delivery of distinct drugs.