Ten patients (6 to 27 years of age) who had severe pancreatic exocrine insufficiency due to cystic fibrosis were studied to determine whether cimetidine would improve dietary fat and nitrogen absorption. When a constant diet was consumed and oral pancreatic enzymes were administered, the addition of cimetidine (150 or 200 mg taken orally one-half hour before meals) signficantly reduced fecal fat excretion from 25.3 +/- 2.9 to 17.3 +/- 2.1 gm/24 hours and fecal nitrogen excretion from 4.5 +/- 0.6 to 3.4 +/- 0.5 gm/24 hours (P less than 0.05). Lower doses of cimetidine resulted in less significant reductions of steatorrhea and azotorrhea. Cimetidine may be a useful adjunct to oral pancreatic enzyme therapy in patients with cystic fibrosis who continue to have steatorrhea and azotorrhea with enzyme therapy alone.