OBJECTIVE To examine populations with diagnosed clinical interstitial cystitis (IC) and urethral syndrome and normal controls using the potassium sensitivity test (PST), to determine the incidence of PST-provoked pain and/or urgency, and to document the type and location of IC and urethral syndrome pain, association of pain with sexual intercourse, and family history of female urgency/frequency problems. METHODS The PST and a questionnaire were administered to 466 patients with clinical IC, 116 patients with urethral syndrome, and 42 controls. RESULTS The PST was positive in 78% of patients with clinical IC, in 55% of patients with urethral syndrome, and in 0% of the controls. Of the patients with clinical IC, 9% responded to the PST with pain only and 8% with urgency only. Patients with clinical IC reported the pain as dysuria (58%), urethral/vaginal (76%), above the pubic bone (53%), lower abdomen (47%), lower back (35%), vaginal (51%), and inguinal (28%). The results were similar for patients with urethral syndrome. Of the sexually active men and women, 71% with clinical IC and 59% with urethral syndrome reported pain associated with intercourse. Urgency/frequency problems in female relatives were reported by 35% of patients with IC and 33% of those with urethral syndrome. CONCLUSIONS The significant potassium sensitivity in both patients with clinical IC and those with urethral syndrome and the absence of potassium sensitivity in normal controls indicates that a positive PST suggests the presence of an abnormal bladder epithelium. The lower rate of positive PSTs in patients with urethral syndrome reflects the less severe, more intermittent, nature of the symptoms in urethral syndrome (early IC). Pelvic pain of bladder origin may occur anywhere in the pelvis. Finally, IC appears to have a genetic component.