Over an 18-month period at a single clinic, 43 new cases of colonic inflammation have been diagnosed (19 proctitis only). Crohn's colitis has been excluded from this analysis. In all these subjects a careful drug history has been taken in a prospective manner and in 4 of these 43 patients colonic inflammation appeared to be directly related to non-steroidal anti-inflammatory drug (NSAID) administration (mefenamic acid, 2; piroxicam, 2). In all 4 patients there was a time interval (mean 3 months) between initiation of treatment with NSAID and presentation with diarrhoea and weight loss. Pathological findings were minor and biochemical changes insignificant, in contrast to the protracted troublesome symptoms. Resolution of symptoms was very rapid on discontinuation of NSAID medication but 2 patients experienced immediate return of symptoms following inadvertent rechallenge. Approximately 10% of newly diagnosed colitis may be related to NSAID administration. Subjects taking NSAID medications appear to be five times more likely to develop colonic inflammation than the general population.