Cross-linked amino acid-containing polyanhydrides based on N-trimellitylimido-beta-alanine (TMA-ala) or N-trimellitylimido-glycine (TMA-gly) and sebacic acid (SA) were synthesized by copolycondensation using 1,3,5-benzenetricarboxylic acid (BTC) prepolymer as a cross-linking agent. Differential scanning calorimetric (DSC) studies of the insoluble copolymers revealed only one sharp melting transition, indicating their cross-linked and/or randomly copolymeric structure. These cross-linked polymers can degrade completely into water-soluble molecules such as amino acids and natural fatty acid, which can be further metabolized by the body. This is an improvement over the photo-cross-linked polyanhydrides reported in the literature, whose cross-links hydrolyze to poly(methacrylic acid), a non-degradable and nonmetabolizable macromolecule with limited biocompatibility. The cross-linked polymers were mixed with p-nitroaniline (PNA) and compressed into discs. In vitro degradation and solute release into physiological media were quantified for up to 70 It. Results showed that, relative to their linear counterparts, cross-linking has little effect on the degradation and solute release of these specific polymers. (C) 2004 Elsevier Ltd. All rights reserved.