Pancreatic enzyme replacement may fail to achieve a beneficial effect because of enzyme inactivation by gastric acid. In this controlled randomized study, 8 hospitalized patients with severe exocrine pancreatic insufficiency and considerable steatorrhoea (greater than 15 g faecal fat/day) were treated with a conventional pancreatic enzyme preparation (Pankreon 700; 3 X 3 dragees daily), with (300 mg) and without cimetidine before meals, and with a new pH-sensitive enzyme preparation (Kreon; 3 X 6 capsules daily) comprising acid-protected granules. Both conventional enzyme replacement plus cimetidine, and acid-protected pancreatin were significantly (p less than 0.05) more effective than conventional enzyme therapy alone. Since both regimens are equally potent in overcoming gastric acid-induced enzyme inactivation, it is concluded that therapy with acid-protected pancreatin may simplify and improve treatment of exocrine pancreatic insufficiency in the presence of gastric hyper- or normo-acidity.