We present a method for attributing a measure of reliability to a residue pair in an optimal alignment of two protein sequences. Validation based on a database of structurally correct alignments [Pascarella and Argos (1992) Protein Engng, 5, 121–137] shows that correctly aligned parts of a sequence alignment systematically receive high scores in this measure. The higher the sequence similarity between two sequences, the larger is the fraction found of the correct parts of the alignment. We used these observations to design a program that draws a reliability curve along an optimal alignment reflecting the chances for each residue pair to be aligned correctly.