Collagenous colitis is associated with normal endoscopy examination and peculiar histopathological changes. The natural history and optimal treatment are not well defined. Our objectives were to analyze the symptomatology of collagenous colitis, determine the natural history, and response to treatment. All patients with collagenous colitis from 1978 to 1992 were studied. Demographic data, symptomatology, associated conditions, colonoscopic findings, and pathology specimens were reviewed. Clinical improvement was classified as none, partial, or complete. Nineteen patients were identified, mainly white females over age 50. Mean follow-up was 22.6 months. Symptom duration was 37 months (range 4 months to 15 years). Symptoms were intermittent diarrhea (19), with a predominant nocturnal component (13); abdominal pain (15); and mild weight loss and incontinence (8). Colonoscopy was normal in 12 patients. Segmental mucosal edema and loss of vasculature pattern were present in seven. Antiperistaltic agents were used in 17 patients with no improvement (15), partial resolution (1), and complete resolution (1). Eight nonresponders received sulfasalazine. Responses were none (6) or complete (2). Ten patients received steroids (10-20 mg/day). One failed to respond. Nine initially responded completely but two relapsed. Seven patients who did not respond to any type of treatment improved eventually, two partially and five completely. These patients were younger (54.3 vs 68.3 years, P = 0.04) and symptom duration was shorter (25.4 vs 44.5 months, P = 0.38) than the rest of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)