The relative efficacy of three commercial pancreatic enzyme supplements in improving fat absorption was studied using the [14C]triolein breath test in 12 patients with chronic pancreatitis. Two of the supplements were enteric coated. The one nonenteric coated product was studied twice: with and without ranitidine coadministration. Doses complied with the manufacturers recommendations. Baseline studies included pentagastrin-stimulated gastric acids, 72-hr fecal fat excretion, and [14C]triolein absorption while not on supplementation. Acid outputs were variable (BAO: 0.3-4.1 meq/hr; MAO: 3.5-34.6 meq/hr). Three patients had mild steatorrhea (i.e., less than 10 g/day) and the remaining severe fat malabsorption (56.9 +/- 41.5 g/day). Although fat absorption was significantly improved by all three supplements, the nonenteric coated preparation was most effective (P less than 0.001). However, laboratory analysis demonstrated that lipase content was four times greater, ie, 17,000 IU/4 tablets. Pretreatment with ranitidine failed to further improve the absorption in patients given nonenteric supplements but was effective in those found to have high or normal acid outputs (P less than 0.001). Our results suggest that the recommended dosage of enteric coated preparations is insufficient for adult patients with severe chronic pancreatitis. Secondly, the marked variability of acid secretion in such patients possibly accounts for the variability of results obtained by others on the usefulness of coadministration of antacids and H2 antagonists. Routine measurement of gastric acid secretion status may help optimize the choice and form of pancreatic enzyme supplementation.