OBJECTIVES: To study the safety and efficacy of intravesically administered capsaicin, a C-fiber afferent neurotoxin, in patients with interstitial cystitis (IC). METHODS: A pilot study of intravesical capsaicin therapy was performed on 5 female patients diagnosed with IC using NIDDK criteria. Patients were evaluated with cystoscopy and CMG on initial presentation. Bladder capacity, urinary histamine, PGE2 and substance P were measured before and after treatment. A symptom score, visual analogue pain score and frequency/nocturia charts were completed before treatment and weekly thereafter by each patient. Topical anesthesia (30 mls of 0.5% bupivacaine) was instilled intravesically for 30 minutes prior to each treatment with capsaicin. The initial instillation consisted of vehicle (1% ethanol in normal saline) and subsequent weekly instillations of capsaicin in increasing concentrations (10, 50, 100, and 250 uM solutions in 1% ethanol) were given as tolerated by the patient. RESULTS: Four out of 5 of the patients experienced subjective improvement in both symptom and pain score. Bladder capacity improved in 1 patient and symptoms of frequency and nocturia improved in 2 patients. Urinary histamine and PGE2 revealed no trend between before and after treatment; however, 3 out of 5 of the patients did have a trend to decreased substance P. No complications were noted during the course of this study. CONCLUSIONS: Intravesical capsaicin is a safe and promising treatment for interstitial cystitis. A potential mechanism of action is desensitization of bladder C-fiber afferents which presumably initiate painful sensations in IC patients. Low dose intravesical capsaicin therapy represents a potential treatment option for interstitial cystitis.