The possibility that immune responses to autoantigens may contribute to the development of atopic disease has been largely ignored. In this paper, we describe the chromosomal localization of the gene for squamous cell carcinoma-associated reactive antigen for cytotoxic T cells (SART-1). The SART-1 gene localized to a region of 11q12-13 showing strong linkage to atopy in previous studies. Further analysis of this gene revealed the presence of at least 20 exons of varying lengths and four novel single-nucleotide polymorphisms, one of which resulted in an amino acid substitution. Association analysis in families recruited on the basis of affected sib pairs for asthma reveal significant association for both coding region polymorphisms with atopy. We therefore hypothesize that polymorphic variation within the SART-1 gene may account for individuals developing atopy.