Objectives To examine the interaction of types and numbers of antecedent nonbladder syndromes (NBSs) to seek clues to the pathogenesis of interstitial cystitis/painful bladder syndrome (IC/PBS). Numerous case series have shown IC/PBS to be associated with several syndromes that do not include bladder symptoms. In a previously reported case-control study, we confirmed these findings and found that such nonbladder syndromes often preceded the onset of IC/PBS. Methods Incident female IC/PBS cases (n = 312) and matched controls were compared for 11 antecedent NBSs. The odds ratios (ORs) for IC/PBS according to the number of antecedent NBSs per person were calculated. From this model, each NBS was serially removed, and the calculations for the ORs were repeated using the remaining 10 NBSs. We assessed the types of NBSs included in each subgroup formed by the number of NBSs. Results The ORs for IC/PBS increased with the increasing number of antecedent NBSs. The types of NBSs were interchangeable in calculating these ORs. The distribution of the types of NBSs was skewed, with allergy overrepresented in those with few NBSs, and the classic functional somatic syndromes of fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome overrepresented in those with many NBSs. Conclusions Two main hypotheses were generated. One was that the incidence of a NBS initiated a process that contributed to the emergence of other NBSs and IC/PBS. The second was that each NBS and IC/PBS was a manifestation of a common, shared pathogenesis. It is likely that a well-designed prospective study will be necessary to distinguish between these 2 hypotheses. © 2011 Elsevier Inc.