Objectives. Nitric oxide (NO) is involved in host defense reactions, and NO production is elevated in various inflammatory disorders. We have found very high levels of luminal NO in the urinary bladder of patients with interstitial cystitis. Oral treatment with low doses of L-arginine, the substrate for NO production, has been reported to alleviate symptoms in patients with interstitial cystitis. The aim of our investigation was to evaluate the effect of higher doses of L-arginine in patients with interstitial cystitis and to study the effects of L-arginine on NO production in the bladder. Methods. Nine women (age 69 ± 3 years) with interstitial cystitis were treated daily with 3 or 10 g of L-arginine for 5 weeks. Symptoms were evaluated with an interstitial cystitis symptom score index, and NO production was measured. Patients with stress incontinence (n=18) were used as control subjects for measurement of NO levels. Results. NO concentration in the urinary bladder was markedly elevated in the patients with interstitial cystitis (239 ± 60 ppb) compared with the control patients (15 ± 2 ppb). NO levels did not change in the patients with interstitial cystitis after oral treatment with L-arginine (189 ± 72 ppb). There was no significant change in the symptom scores at either dose after 5 weeks of L- arginine treatment. Conclusions. L-arginine treatment in the doses used in this study did not change NO production in the urinary bladder in patients with interstitial cystitis. Furthermore, the patients in our study did not notice any relief of their symptoms.