The bladder mast cell contains many granules, each of which can secrete many vasoactive and nociceptive molecules. A number of conditions, such as extreme cold, drugs, neuropeptides, stress, trauma, and toxins, can trigger the mast cell to secrete some of its contents; they, in turn, can sensitize sensory neurons, which can further activate mast cells by releasing neurotransmitters or neuropeptides. Additionally, the mast cell can directly cause vasodilation and bladder mucosa damage while also attracting inflammatory cells, thus causing many of the problems seen in interstitial cystitis. The mast cell appears to be involved in the pathogenesis of interstitial cystitis. Although it is not pathognomonic of the disease, mastocytosis does occur in a significant subset of interstitial cystitis patients. Because interstitial cystitis is now regarded as a syndrome caused by multiple factors, it is conceivable that one cause of interstitial cystitis is associated with bladder mastocytosis and mast cell activation. The fact that mast cells are also increased in patients with transitional cell carcinoma of the bladder does not diminish the importance of mastocytosis in interstitial cystitis, because the mast cells are not activated in carcinoma but are activated in interstitial cystitis. Perhaps the common strand between these two bladder diseases is the putative allergens/carcinogens in bladder urine that breach the protective lining of the bladder and then elicit an immune response in the bladder wall. Furthermore, the majority of patients with a history of bladder tumors receive multiple courses of intravesical chemotherapy (such as thiotepa) or immunotherapy (bacille Calmette-Guerin), and it is possible that these agents damage the bladder lining or provoke an inflammation in the bladder wall. The theory of a defective/deficient bladder glycosaminoglycan layer in interstitial cystitis is also consonant with this putative chain of events in the pathogenesis of interstitial cystitis. Thus these two theories interstitial cystitis causation--a glycosaminoglycan deficiency and bladder mastocytosis--may well operate in concert to cause bladder inflammation and the symptoms of interstitial cystitis. Clinicians may be at a distinct disadvantage because they are faced with a multitude of potential mast cell triggers and numerous mediators secreted. It may, therefore, be advisable to block or inhibit the mast cell from responding to many of these various stimuli. Specific mast cell mediators should be assayed as possible diagnostic tools, and potential mast cell inhibitors should be tried under controlled conditions to determine the extent of therapeutic benefit.