The purpose of this study was to perform a randomized, prospective comparison of corticosteroid enemas (CS--100 mg of hydrocortisone/60 cc P.R. q.h.s.; n = 12), mesalamine enemas (5-ASA--4 g/60 cc P.R. q.h.s.; n = 19), and short-chain fatty acid enemas (SCFA--60 cc P.R. b.i.d.; n = 14) for the treatment of proctosigmoiditis. Patients presenting to the Ferguson Clinic with the diagnosis of idiopathic proctosigmoiditis were evaluated for age, sex, prior history of proctitis, duration of symptoms prior to presentation, endoscopic scoring, and mucosal biopsies. Clinical evaluation was performed at two-week intervals for six weeks, with repeat biopsies taken at six weeks. There was no significant difference with respect to age, male/female ratio, past history of proctosigmoiditis, length of colorectum involved at the time of initial presentation, symptom resolution, and endoscopic and histologic improvement among the three treatment groups. Recovery occurred in a similar proportion in each of the three groups: CS, 10/12; 5-ASA, 17/19; and SCFA, 12/14. The cost of six weeks of treatment was: CS, $71.82; 5-ASA, $347.28; and SCFA, $31.50. This study indicates that SCFA enemas are equally efficacious to CS or 5-ASA enemas for the treatment of proctosigmoiditis at a significant cost savings.