1. Central nervous system muscarinic receptors have been implicated in genetic models of hypertension as well as in stress adaptive cardiovascular responses. To determine if the sequence of the M1-muscarinic receptor is pathogenetic for hypertension, we analysed the differences between SHRLJ (spontaneously hypertensive rats) and WKYLJ (Wistar-Kyoto) rats in the sequence of the M1-receptor gene. 2. Specific primer sets were synthesized so as to cover the gene in 10 fragments (158-344 base pairs) with overlaps. Analysis was conducted by both polymerase chain reaction (PCR)-acrylamide and by single-stranded conformation polymorphism (SSCP). 3. No polymorphic locus was found by non-denaturing PCR-acrylamide nor by denaturing SSCP. Slight intrastrain variations in fragment 2 of the parental strains were examined by direct sequencing; however, no difference in sequence was found between SHRLJ and WKYLJ. To identify the chromosomal location and possible linkage with a polymorphic locus, rat/mouse somatic hybrid cell lines were examined. The rat M1-muscarinic receptor was assigned to chromosome 1. 4. Based on analysis of the coding sequence of the gene, our data do not support the hypothesis that the M1-muscarinic receptor is a candidate gene for hypertension. We conclude that, pending analyses of the promoter and regulatory regions of the gene, differences in the M1-muscarinic receptor in SHR either in receptor expression or in physiological response must be due to altered intracellular signalling or extracellular transynaptic events, but not due to a mutation of the gene sequence.