Bladder muscle specimens from 7 patients with neurogenic bladder dysfunction were analyzed to determine whether the muscarinic receptor subtype mediating contraction shifts from M₃ to the M₂ subtype as found in the denervated, hypertrophied rat bladder. Seven bladder specimens were analyzed from 6 female and 1 male patients. Six of the patients had traumatic cervical spinal cord injuries (C4-C7) and the other had an L1 congenital myelomeningocele. This was compared to results from bladder specimens obtained from 8 organ transplant donors. The affinities of 3 subtype selective muscarinic receptor antagonists for inhibition of carbachol induced contractions were determined. The affinity of the M₃ selective antagonists darifenacin and para-fluoro, hexahydrosiladifenadol (p-F-HHSiD) was determined in 6 of the 7 spinal injury patient specimens. The affinity was consistent with M₂ mediated contractions in 4 of these 6 specimens, intermediate between M₂ and M₃ in one specimen and within the M₃ range in one specimen. The other specimen, tested only with the M₂ selective antagonist methoctramine, showed an M₃ affinity. In the organ donors, the affinity of p-F-HHSiD was within the M₂ range for 6 of 7 specimens whereas the affinity of darifenacin was within the M₃ range for 5 out of 6 and intermediate between M₂ and M₃ for the other specimens tested. The affinity of methoctramine in both organ donor specimens tested was within the M₃ range. Whereas normal detrusor contractions are mediated by the M₃ receptor subtype, in patients with neurogenic bladder dysfunction as well as certain organ transplant donors, contractions can be mediated by the M₂ muscarinic receptor subtype.