Collagenous colitis and lymphocytic colitis cause chronic watery diarrhea. Multiple therapies have been found to improve symptoms but there have been few long-term follow-up studies. Our goal was to obtain long-term clinical follow-up on a cohort of patients with independently confirmed typical histopathologic changes. Pathology slides from 32 cases of collagenous or lymphocytic colitis patients from 1988-1992 were independently reviewed. Twenty-five cases were confirmed by both groups of pathologist as collagenous or lymphocytic colitis. For these 25 patients, charts were reviewed and telephone follow-up interviews were performed in 1992 and 1995. Seven of 32 (22%) of the original cases were not confirmed on independent pathologic interpretation. A 15.8% discordance rate was found between the different groups of pathologists. Patient demographics were similar to previously published reports except one-half of our patients had diarrhea of only 6 months or less. Eighty-one percent of patients receiving 5-ASA agents reported improvement as well as 100% of those receiving prednisone. At 23 month follow-up 86% of patients reported improvement in diarrhea and only 32% required routine medications. At 47 month follow-up all patients reported improved diarrhea and only 29% required routine medications. Collagenous and lymphocytic colitis can sometimes be identified in patients with relatively brief duration diarrhea. Clinical parameters and response to therapy are similar for collagenous or lymphocytic colitis. Most patients with lymphocytic and collagenous colitis improve with therapy such as 5-ASA preparations or steroids. Over a follow-up period of several years, most patients have improvement in diarrhea and generally do not require maintenance medications. Independent pathologic confirmation of the diagnosis should be obtained in patients not responding to therapy.