Antithrombin is the principle regulator of thrombin and other blood coagulation proteinases. It is a member of the serpin family of proteinase inhibitors. The genomic sequence of the antithrombin locus has been completed, revealing a gene spanning 13,477 base pairs from the transcription start site to the poly(A) addition signal. Nine complete and one partial Alu repeat elements were identified within the introns of the gene, with all but one orientated in the reverse direction. Inherited deficiency of antithrombin is associated with a venous thrombotic tendency. Restriction fragment mapping of the antithrombin genes in an individual with type I antithrombin deficiency identified an intragenic deletion in one allele. Localization of the deletion breakpoints involved restriction analysis and direct sequencing of amplified DNA spanning the deletion site. The deletion removed 2761 base pairs, affecting exon 5 and flanking introns, with the deletion ends contained within the left components of two Alu elements. It is likely, therefore, that the deletion arose by homologous recombination between the two Alu elements.