The response of the urinary bladder body and base to autonomic agents was studied in streptozocin (STZ)-diabetic rats. The bladder body region from 6-wk diabetic rats showed no changes in response to acetylcholine, phenylephrine, or isoproterenol. In contrast, the bladder base region showed a 39% increase in contractile response to acetylcholine and a 37% increased response to phenylephrine. In tissues from 47-wk diabetic animals, the bladder body showed a 51% increased contractile response to acetylcholine and a 37% increased relaxation response to isoproterenol. The bladder base showed a 66% increased contraction to acetylcholine. Thus, in the bladder base, enhanced responses to acetylcholine are detected soon after induction of diabetes and continue to increase as the diabetic state progresses. Moreover, in the same bladder region, an increase in responsiveness to alpha-adrenergic stimuli occurs. In the bladder body, enhanced responses to cholinergic and to beta-adrenergic stimuli occur, but are only observed in a more chronic diabetic state. The data suggest that an effect associated with autonomic diabetic neuropathy of the urinary bladder is an increased postsynaptic responsiveness to cholinergic stimuli in both regions.