A method for optimally locating gaps in the amino acid sequences of homologous proteins is presented. The method involves three steps: (1) demonstration that the sequences are indeed homologous, (2) location of regions where the homologous pairing is reasonably certain, and (3) location of gaps between these regions so as to minimize the total number of mutations required to account for the differences between the two sequences. The major virtues of this procedure are that the assertion of homology does not depend upon the prior introduction of gaps and that a genetic rather than a chemical test is the basis for asserting a genetic relationship.