The failure of bethanechol chloride to induce voiding in patients with neurogenic bladder, despite a positive bethanechol test, is being reported more frequently. An experimental model was designed in the cat to study the response of the bladder and urethra to subcutaneous and intraarterial bethanechol after complete and partial sacral decentralization. Complete sacral rhizotomy abolished the micturition reflex. Basal urethral perfusion pressure was not affected by complete sacral rhizotomy and a significant part of this basal urethral pressure remained sympathetically mediated. However, the urethral constriction response to bladder filling was lost in half the cats with complete lesions. Bladder and urethral supersensitivity to bethanechol chloride in cats with complete lesions was characterized by a shift to the left of the i.a. dose-response curve, and by the presence of responses to doses of s.c. bethanechol chloride which are subthreshold in normal cats. The urethra also showed exaggerated constriction responses to i.a. and s.c. bethanechol. After complete lesions a part of the bladder and urethral responses to s.c. bethanechol was adrenergically mediated and exerted through the vesicourethral short neuron system. The rest of the response was due to stimulation of urethral muscarinic receptors. Partial sacral lesions were compatible with a micturition reflex and the urethra retained its reflex response to bladder distension. After partial decentralization the bladder and urethra also showed responses to subthreshold doses of s.c. bethanechol. While the bladder response to s.c. bethanechol did not show a significant adrenergic component in cats with partial lesions, most of the urethral response was sympathetically mediated. In conclusion, complete cauda equina lesions result in an areflexic detrusor with frequent loss of the urethral responsiveness to bladder filling. Urethral supersensitivity to s.c. bethanechol might be responsible for a non-voiding outcome after bethanechol injection in patients with complete cauda equina lesions, despite a positive bethanechol test. Because the detrusor reflex is preserved and the urethra is less supersensitive to bethanechol after partial cauda equina lesions, these may represent a better indication for bethanechol therapy than do complete ones.