IMGT/DomainGapAlign is the online tool of IMGT(®), the international ImMunoGeneTics information system(®), for the analysis of amino acid sequences and two-dimensional (2D) structures of domains. IMGT/DomainGapAlign allows the analysis of the closest variable (V) and constant (C) domains of immunoglobulins (IG) or antibodies, T cell receptors (TR), and immunoglobulin superfamily (IgSF) proteins, and of the groove (G) domains of major histocompatibility (MH; in humans, HLA for human leukocyte antigen) and MH superfamily proteins. IMGT/DomainGapAlign aligns the user own sequences against the IMGT domain reference directory, displays amino acid changes, creates IMGT gaps, and delimits the domain strands and loops (and helix for G domain) according to the IMGT unique numbering. IMGT/DomainGapAlign is coupled to the IMGT/Collier-de-Perles tool that draws standardized IMGT Colliers de Perles. The analysis is based on the IMGT-ONTOLOGY concepts of identification, classification, description, and numerotation generated from the axioms of the Formal IMGT-ONTOLOGY or IMGT-Kaleidoscope. IMGT/DomainGapAlign provides an invaluable help for antibody engineering and antibody humanization as it precisely defines the standardized framework regions (FR-IMGT) and complementarity determining regions (CDR-IMGT) to be grafted. IMGT/DomainGapAlign is freely available at http://www.imgt.org.