Detrusor specimens were obtained from 5 patients affected by interstitial cystitis (IC) and 5 patients with bladder carcinoma (controls). Muscle strips were prepared for in vitro pharmacological studies. In all detrusor strips taken from IC patients, an important portion of the electrically-induced contraction was atropine-resistant. In contrast, atropine-resistance was never observed in control detrusors. H1 and H2 antagonists did not affect noncholinergic contractile response which, conversely, was abolished following desensitization to alpha, beta methylene ATP (APCPP). Detrusor muscle from patients affected by IC exhibited an increase in sensitivity to APCPP and a decrease in sensitivity to acetylcholine with respect to control detrusor. Taken together these results are consistent with the presence of a purinergic neurotransmission in parasympathetic nerve terminals of the urinary bladder affected by IC, probably as a consequence of alterations in the innervation and/or electrical coupling between smooth muscle cells. The sensitivity of IC detrusor muscle to histamine was much lower than that of control detrusor, suggesting a desensitization of histamine receptors present in the bladder wall of IC patients.