The purpose of this study was to screen a general patient population for interstitial cystitis (IC) and to determine the outcome of combination therapy (pentosan polysulfate sodium [PPS] and hydroxyzine) in newly diagnosed patients. Screening for IC symptoms was performed on 3883 patients (>or=18 yr of age). After further evaluation, a diagnosis of IC was made in 160 patients. These patients were subsequently treated with PPS 200 mg twice a day (off-label usage) and hydroxyzine hydrochloride 25 mg nightly for 1 to 12 mo. Clinically meaningful (>or=50%) improvement in IC symptoms, as measured by the Patient's Overall Rating of Improvement of Symptoms index, was reported by 59 of 122 patients (48.4%) who completed 1 mo of therapy. This effect was sustained for 12 mo in 26 of 28 patients (92.9%) completing the study. The combination of PPS and hydroxyzine hydrochloride was well tolerated and effective in relieving symptoms associated with IC.