Abstract Summary: We introduce an algorithm that uses the information gained from simultaneous consideration of an entire group of related proteins to create multiple structure alignments (MSTAs). Consistency-based alignment (CBA) first harnesses the information contained within regions that are consistently aligned among a set of pairwise superpositions in order to realign pairs of proteins through both global and local refinement methods. It then constructs a multiple alignment that is maximally consistent with the improved pairwise alignments. We validate CBA's alignments by assessing their accuracy in regions where at least two of the aligned structures contain the same conserved sequence motif. Results: CBA correctly aligns well over 90% of motif residues in superpositions of proteins belonging to the same family or superfamily, and it outperforms a number of previously reported MSTA algorithms. Availability: CBA is available at and the source code is freely available at Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.