Abstract Purpose We investigated the role of Tamm-Horsfall protein in interstitial cystitis. Materials and Methods Urinary Tamm-Horsfall protein excretion was analyzed in interstitial cystitis patients and controls, and bladder biopsy specimens were stained immunohistochemically for Tamm-Horsfall protein. Results Urinary Tamm-Horsfall protein levels in 28 women with interstitial cystitis were statistically significantly greater than those in 25 female controls. No positive staining for Tamm-Horsfall protein was demonstrated in the bladder tissue from 10 interstitial cystitis cases. Conclusions The results support the notion that interstitial cystitis may have a systemic etiology. In addition, this assay might have clinical value in the diagnosis of interstitial cystitis.