It has been hypothesized that urine from interstitial cystitis (IC) patients may contain one or more toxic factors not present in "normal" urine. Bladder tissues exposed to these toxic factors could have elevated stress proteins. If this assumption is correct, stress protein levels could be a useful marker for identifying patients at risk for developing this syndrome. To experimentally investigate this possibility, a sensitive assay (ELISA) was used to measure levels of the 72 kDa stress protein in urothelial target cells after in vitro exposure to urine from IC patients. We observed a modest 12% increase in 72 kDa stress protein in cells treated with urine from IC patients compared to cells exposed to normal urine (1.12 compared to 0.99 ng/microg extracted protein; P < 0.05). In addition, it was possible to demonstrate the 72 kDa stress protein in histologic sections obtained from mucosal biopsies of IC patients. Stress protein was located primarily in the surface urothelial cells of the mucosa. These results seem to indicate that stress protein could play an important protective role at this particular site. They further suggest that IC urine is more toxic than normal urine and, in contact with underlying urothelial and deeper bladder tissue, may upregulate genes involved in stress protein responses. This may be an important concept in the etiology of IC.