A review of 29 patients with toxic megacolon complicating ulcerative colitis was undertaken to (1) compare the results of medical and surgical treatment; (2) determine the optimal timing for surgical intervention, and (3) identify possible precipitating factors. Twenty-one patients were treated medically with nasogastric suction, steroids, parental fluids, blood transfusions, and antimicrobial agents. Of the 21 patients, 11 (53%) showed improvement by subjective and objective criteria and 10 (47%) failed to respond. Sixteen patients were treated surgically. This group was subdivided into 8 patients who failed to respond to medical treatment and 8 treated surgically. Total proctocolectomy with ileostomy was performed in 8 and subtotal colectomy and ileoproctostomy in 8, with subsequent proctectomy and ileostomy in 6 patient. Six of 8 patients (75%) treated primarily surgically improved, and 2 (25%) died. Seven of 8 patients (87.5%) treated surgically after failure of medical trial showed definite postoperative improvement, and 1 (12.5%) failed. Those who were operated on within the first 48-72 hr after the diagnosis of toxic megacolon was made responded uniformly well. Anticholinergics, opiates,, barium enema, and colonoscopy were identified as possible precipitating factors in 70% of cases. The results of this tudy in this patient population indicate that early surgical therapy in toxic megacolon is associated with better results than medical therapy (P less than 0.025). Although intensive, optimal medical therapy plays a significant role in the management of toxic megacolon, failure to induce rapid improvement within 48-72 hr constitutes an indication for definitive surgical treatment.