Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic condition of unknown etiology manifested by a constellation of symptoms including bladder, urethral, and/or pelvic pain, irritative voiding symptoms (urgency, frequency, nocturia, dysuria), and the absence of known etiologies such as recurrent urinary tract infection. It is estimated to afflict 37 to 67 per 100,000 individuals in the US (or possibly many more), with a marked female predilection, resulting in substantial morbidity, time lost from work, and medical costs. An improved understanding of the pathogenic mechanisms underlying IC/PBS could lead to new diagnostics and therapeutic and preventive strategies directed at this debilitating illness. The goal of this epidemiologic project is to reexamine the role of bacterial or viral agents in women with IC/PBS by combining a prospective sample-collection study with quantitative microbiology, a novel mass spectrometric assay, and a microarraybased viral screening technique. These analytical approaches are motivated by recent findings suggesting that tissue-adherent bacterial forms may be associated with low-level or intermittent bacteriuria and that a number of unexplained inflammatory conditions may be caused by as yet undescribed or unexpected viral infections. In this project, we will prospectively follow cohorts of women with IC/PBS for 6 months and agematched women without IC/PBS for 3 months. During this study period, subjects will maintain a daily personal diary and collect simultaneous weekly midstream urine and vaginal swab specimens. In Specific Aim 1. we hypothesize that a subset of IC/PBS is caused by bacterial infections associated with low-grade or intermittent bacteriuria or by unappreciated viral pathogens. We will compare IC/PBS patients with agematched controls. In Specific Aim 2. we hypothesize that IC/PBS symptom exacerbations are associated with the new appearance, or an increased population, of uropathogenic bacteria or viruses. In these studies, we will use the study's longitudinal design to determine whether different measures of infection correlate with periods of high and low degrees of IC/PBS symptoms. In summary, data concerning the role of infection in the pathogenesis of IC/PBS remains fragmented and contradictory, even though there are striking similarities between women with IC/PBS and those with recurrent DTI. We propose a novel approach based on recent developments in urological infection pathophysiology to address the important question of whether microbial pathogens are involved in IC/PBS. Results of this study will yield important information on the pathogenesis of IC/PBS and potentially result in better therapeutic and preventive strategies.