We evaluated the bentiromide test by analyzing para-aminobenzoic acid (PABA) in plasma and urine (a) for the identification of patients with complete pancreatic insufficiency and (b) as an alternative to the secretin-cholecystokinin test. Nine control subjects, 18 patients with cystic fibrosis, and 4 patients with Shwachman's syndrome were studied. Based upon the secretin-cholecystokinin test, pancreatic function was judged to be < 0.1% of normal in 7 patients with cystic fibrosis and malabsorption and between 0.7% and 90% of control values in 11 patients with cystic fibrosis and 4 patients with Shwachman's syndrome without malabsorption. The bentiromide test was performed in two stages: first with bentiromide alone, then with equimolar free PABA. After ingestion of free PABA, the plasma profile and urinary excretion of PABA were comparable in controls, patients with cystic fibrosis, and patients with Shwachman's syndrome. Thirty minutes after oral bentiromide, plasma PABA values in patients with and without malabsorption were significantly lower than in the control group. From 60 to 180 min after ingestion, plasma PABA levels in patients without malabsorption were no different from controls; whereas levels in patients with malabsorption were significantly lower than in controls and in those without malabsorption, reaching the highest significance at 90 min. Similar results were obtained when the urinary excretion of PABA was considered. Only the 90-min plasma test reliably detected cystic fibrosis patients with steatorrhea, however. Duodenal colipase output was highly correlated with both the 90-min plasma test and the urinary excretion of PABA, with similar results for lipase and trypsin output. Reliable detection of pancreatic dysfunction, nevertheless, was not obtained even with the plasma test, in cystic fibrosis patients with > 5%-10% of the mean normal enzyme output. In patients with Shwachman's syndrome, none of whom had malabsorption, the plasma and urinary test failed to detect pancreatic dysfunction even with enzyme output as low as 1% of normal.