We analyzed the presence of the cytokine interleukin-6 in urine samples from interstitial cystitis patients. Interleukin-6 was significantly elevated in patients with interstitial cystitis (169.29 +/- 90.81 pg./ml. versus 34.8 +/- 6.35 pg./ml. in controls). Representative urine samples were analyzed with specific antibody to interleukin-6 and greater than 80% of the biological activity was neutralized. These cytokine measurements were then compared with clinical parameters and interleukin-6 levels correlated positively with the pain scores. Studies on the potential cellular origin of interleukin-6 showed increased levels in spontaneously voided urine but not in ureteral urine, which was collected during cystoscopy, suggesting that interleukin-6 is the product of activated cells in the bladder. This finding is supported by in situ hybridization analyses, which showed that interleukin-6 messenger ribonucleic acid expressing cells are located in the interstitium and epithelial layer, and within blood vessels. The implications of these findings for interstitial cystitis pathogenesis are discussed.