FUGUE is a program for recognizing distant homologues by sequence-structure comparison. It utilizes environment-specific substitution tables and structure-dependent gap penalties, where scores for amino acid matching and insertions/deletions are evaluated depending on the local environment of each amino acid residue in a known structure. Given a query sequence (or a sequence alignment), FUGUE scans a database of structural profiles, calculates the sequence-structure compatibility scores and produces a list of potential homologues and alignments.