Background: Muscarinic acetylcholine receptors are members of the superfamily of G protein-coupled, 7 transmembrane-spanning proteins. They are important in the development of airway hyperresponsiveness. In the lung the M-3 receptor, encoded by the cholinergic receptor muscarinic 3 gene, is present in airway smooth muscle and mediates smooth muscle contraction. Objective: We considered the cholinergic, receptor muscarinic 3 gene as a possible candidate gene for bronchial asthma and initiated studies to identify polymorphisms in the promoter region. Method: We identified 4 single-nucleotide polymorphisms; (-708A/G, -627G/C, -513C/A, and -492C/T) and 2 short tandem repeat polymorphisms, a tetranucleotide (CTTT)(12-20) and a dinucleotide (GT)(6-19) repeat. Results: None of the identified single nucleotide polymorphisms were significantly more frequent in asthmatic patients (n = 76) compared with in healthy control subjects (n = 81). Furthermore, there was no evidence for nonrandom transmission of short tandem repeat polymorphism haplotypes to individuals with asthma or bronchial hyperresponsiveness (P > .50) in a large Hutterite pedigree. However, there was significant nonrandom transmission of haplotypes to individuals with skin test reactivity to cockroach allergens (global transmission disequilibrium test: chi(2) = 38.55, P =.013). Conclusions: These results suggest a possible role for this gene in atopic disorders. (J Allergy Clin Immunol 2003;111:527-32.).