Conventional oral pancreatic enzyme preparations are largely inactivated by gastric acid. To circumvent this, preparations containing pancreatic enzymes in the form of microspheres encoated by a pH-sensitive membrane have been introduced. We compared the therapeutic efficacy of two such preparations, Pancrease (mean ± 2SD, lipase activity/capsule 4933 ± 140 units) and Cotazym-S (lipase activity/capsule 5712 ± 152 units), with a conventional pancreatic enzyme preparation, Pancreatin (lipase content/tablet 684 ± 52 units) in seven men with pancreatic insufficiency secondary to alcoholism. In each patient, we collected stool for 72 hours for total lipid determinations without pancreatic enzyme therapy, and on various pancreatic enzyme preparations. At the end of the study, we asked patients which oral pancreatic enzyme preparation they preferred. Fecal fat excretion was significantly reduced with Pancrease and Cotazym-S as compared to the untreated state (p < 0.0005). Pancrease and Cotazym-S were equally effective in reducing fecal fat excretion. There was a trend towards greater reduction of fecal fat excretion with the pH-sensitive enteric coated preparations than with a weak conventional pancreatic enzyme preparation with low lipase content. The difference, however, was not statistically significant. The frequency of bowel movements per day was similar on treatment with both pH-sensitive enteric coated preparations. Our patients preferred encapsulated enteric coated preparations to the tablets of conventional pancreatic enzyme preparation for palatability and the smaller number of capsules to be taken with each meal.