A temperature-sensitive hydrogel based on a copolymer of BSA and poly(N-isopropylacrylamide) (PNIPAAm) has been synthesized using carbodiimide chemistry. Fourier transform infrared spectroscopy confirmed primary complex formation between carbodiimide-activated carboxylic acids on the protein with protein amino groups. As a result of temperature-induced conformational changes in PNIPA Am grafted onto the protein backbone, these protein hydrogels show significant morphological changes in response to temperature. The structural changes of the gels in response to temperature were assessed using scanning electron microscopy, and the effect of temperature on their balance of hydrophobicity was found using turbidity measurements. Composite pore-filled membranes formed by impregnating glass fiber filters with the polymer mixture prior to gelation were used to determine permeability changes in response to temperature using both low (riboflavin) and intermediate (lysozyme) molecular weight diffusates. Clear correlation was found between changes in morphology, turbidity, and gel permeability as the gel temperature was increased from 24-37 degrees C. In the case of permeability studies, significant transport of lysozyme only Occurred at temperatures above the lower transition temperature of the hydrogel, suggesting the gel was acting as a mechanical "valve" to control flux. (C) 2008 Wiley Periodicals, Inc. Adv Polym Techn 27: 27-34, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20113