Thermo- and pH-responsive microgels were prepared from solubilized native elastin by crosslinking of the elastin lysine residues with poly(ethylene glycol) diglycidyl ether (PEG-DGE) and with bis(sulfosuccinimidyl) suberate (BS3). In the first case, a peptide-PEG conetwork was obtained whereas, in the second case, the elastin peptides were interlinked with hydrophobic bridges. The structure of the microgels was controlled by the ratio of crosslinker to elastin and by performing the crosslinking reaction in an inverse minielemulsion, yielding particles with a diameter in the submicron range. Depending on the degree of crosslinking, the hybrid microgels exhibited a volume change transition at 37 and 35.5 degrees C and pH responsivity in the range of 5-7 for microgels crosslinked with PEG-DE and BS3, respectively. This temperature- and pH-responsive behavior can be assigned to the well-investigated coacervation of elastin peptides, demonstrating that the elastin functionality is abolished only by rather dense crosslinking. In spite of the broad distribution in the molecular weight of the elastin molecules, the microgels remained soluble. Light scattering and sedimentation experiments demonstrated that the coacervation occurred predominantly intramolecularly, i.e., by collapse in the core while the corona stabilized the colloidal dispersion against precipitation. Preliminary experiments were conducted to evaluate the suitability of these microgels for use as a drug-release system and demonstrated cytocompatibility, enzymatic degradability by elastase, and entrapping and slow release of a water-soluble biopolymer (Texas Red-labeled dextran with M-w = 70,000). In summary, we present an easy entry to functional biohybrid microgels, where the responsiveness to temperature and pH can be exploited further for application of the microgel as a drug carrier.