Objectives: No diagnostic physical signs, urologic findings, or laboratory tests are available for interstitial cystitis/painful bladder syndrome (IC/PBS). Its diagnosis is determined by symptoms and the exclusion of mimicking diseases. We hypothesized that certain pain characteristics are sensitive criteria for diagnosing IC/PBS. Methods: In women with recent-onset IC/PBS recruited in 2004 to 2006 for the case-control study, "Events Preceding Interstitial Cystitis," we identified the locations of each patient's pain and in a nonleading way asked about the effects of 17 different experiences (criteria) on the pain. We identified a set of criteria that described the largest number of patients in the Events Preceding Interstitial Cystitis study. In a secondary analysis of another cohort recruited by others in 1993 to 1997, the Interstitial Cystitis Database, we determined the proportion of patients captured by these same criteria. Results: In the Events Preceding Interstitial Cystitis study, pain that worsened with a certain food or drink and/or worsened with bladder filling and/or improved with urination was reported by 151 (97%) of 156 patients. These were the only three criteria that applied directly to the bladder. The same three criteria described the pain of 262 (97%) of 270 women in the Interstitial Cystitis Database who "definitely" had IC/PBS. Conclusions: An hypothesis generated in one IC/PBS patient group and tested in another-pain that worsened with certain food or drink and/or worsened with bladder filling and/or improved with urination-was described by 97% of the patients with IC/PBS in each cohort. This triad might describe the pain of IC/PBS and contribute to a sensitive case definition. Estimating specificity awaits comparison with other diseases with similar symptoms. © 2008 Elsevier Inc. All rights reserved.