Many tests are available to assess pancreatic function. The ideal test would be simple and have adequate sensitivity in mild to moderate chronic pancreatitis (MCP) and severe CP (SCP). Fecal pancreatic elastase 1 (FPE1) assay (ScheBo Tech) has been proposed as a reliable test to evaluate pancreatic exocrine function, with sensitivities of up to 100% in diagnosing CP. Cutoff values (microgram/g stool) of < 100 have been suggested as SCP, 100-200 as MCP, and > 200 as normal. The test's ability to detect MCP distinguished by the absence of steatorrhea, and its specificity among various etiologies of malabsorption, has not been fully evaluated. The aim of this study was to evaluate this assay in subjects including patients with SCP with steatorrhea, patients with MCP with no steatorrhea, healthy controls, and diseased controls with nonpancreatic malabsorption. Thirty-six subjects [15 healthy controls, 7 malabsorption controls, and 14 subjects with CP (7 MCP, 7 SCP)] had FPE1 assays. One hundred fifty-four assays for FPE1 were run for analysis. The intraassay and interassay intraclass correlation coefficients were 0.93 and 0.90, respectively. All SCP had values of < 100 micrograms/g but more than half of the MCP subjects had FPE1 levels within the normal range. The subjects with nonpancreatic malabsorption had FPE1 values ranging from 55 to > 500 micrograms/g of stool. Although the assay detected SCP with steatorrhea, it did not consistently separate the MCP patients from normals. The majority of those with nonpancreatic malabsorption had false-positive values. These results may differ from previously described data because of the purposeful inclusion of MCP subjects, documented by the lack of steatorrhea, and the inclusion of disease controls with nonpancreatic malabsorption. Although PE1 concentrates in the stool and is not significantly degraded, subtle changes in this enzyme, as in MCP, do not seem to be detectable by this assay. This group continues to be the most difficult group to diagnose clinically.