The phase behavior of a biocompatible binary polyanhydride blend system composed of poly[ 1,6-bis(p-carboxyphenoxy)hexane] (poly(CPH)) and poly(sebacic acid) (poly(SA)) is described. The phase behavior is determined from the CPH-SA segmental interaction parameter, chi, obtained from in situ small angle X-ray scattering (SAXS) experiments. The predicted phase diagram has an upper critical solution temperature (UCST) with a critical point of 114 degreesC. The phase diagram is validated by optical microscopy (cloud point determination) of blend films. However, the full range of blend compositions is not accessible via cloud point measurements, because the melting point of poly(CPH) is above the critical point. Additionally, the poly(CPH) crystallinity interferes with cloud point determination because the length scale of the amorphous phase separation and that of the crystallinity are both near the limit of resolution of the optical microscope. The poly(CPH)-rich region of the phase diagram was investigated by ex situ atomic force microscopy on thin blend films. Finally, in order to validate the use of molecular simulations to study energetic and structural properties of this system, chi is also computed from molecular dynamics both above and below the critical point. Excellent agreement is obtained for all three experimental methods and the computational technique. The results are compared to a simple group contribution method for computing the solubility parameters of the polymers. This technique fails to accurately predict the phase diagram. (C) 2004 Published by Elsevier Ltd.