1. Muscarinic receptors are important in the development of airway hyperresponsiveness, and dysfunction of these receptors has been suggested to be present in asthma. 2. The human muscarinic M(2) and M(3) receptor genes were screened for polymorphic variation using single-stranded conformation polymorphism (SSCP) analysis, complemented by direct fluorescent sequencing. Forty-six random DNA samples and 46 respiratory physician diagnosed asthmatic samples were used as a template for analysis. 3. Within the muscarinic M(2) receptor gene, we identified two degenerate single base substitutions (1197T-->C, Thr-->Thr and 976A-->C, Arg-->Arg) in one random and one asthmatic sample respectively. Analysis of the 3' UTR region revealed an additional 'A' at bp 1793 (c.f. ATG). This was present in all of 49 samples analysed by sequencing or BsmI digest, suggesting that the published sequence (GenBank Accession NO: M16404) is incorrect. A common 3' UTR polymorphism (T-->A) was found at bp 1696 (c.f. ATG) (allelic frequency=65%, n=60), but this does not alter transcription factor recognition sites. 4. We were unable to identify any polymorphic variation within the muscarinic M(3) coding region or the flanking regions investigated, using the methods described. 5. The coding regions for the human muscarinic M(2) and M(3) receptor genes are both highly conserved. These data suggest that polymorphic variation within these coding sequences is unlikely to account for inter-individual variability in response to methacholine or anticholinergic therapy. The potential functional significance of the muscarinic M(2) receptor 3' UTR polymorphism (bp 1696) remains to be determined.