Immunoreactive lipase (IRL) was measured in 368 stool samples from 231 individuals by means of a new enzyme-linked immunoabsorbent assay technic, to test its validity as an indicator of exocrine pancreatic insufficiency. Ninety-seven stool samples from 64 healthy volunteers showed a logarithmically normal distribution of IRL values and a median IRL concentration of 17 micrograms/g (range, 2.75-117.3 micrograms/g) with a statistically calculated lower normal limit of 4 micrograms/g. In 100 stool samples from patients with chronic pancreatitis and proven steatorrhea the median IRL concentration of 6 micrograms/g (range, 0.002-107 micrograms/g) was significantly lower than that of normal controls and of 52 stool samples from patients with chronic pancreatitis without steatorrhea (IRL, 40 micrograms/g; range, 0.55-302 micrograms/g), 45 stool samples from 23 patients with celiac disease (IRL, 96 micrograms/g; range, 6.05-563 micrograms/g), and 30 stool samples from 26 patients with chronic diarrhea (IRL, 57 micrograms/g; range, 4.2-573 micrograms/g). It is concluded that fecal IRL is a promising new enzyme test with low diagnostic sensitivity (34%) but excellent diagnostic specificity (98%) in chronic pancreatitis and for diagnostic study of chronic diarrheal disorders. In contrast to fecal chymotrypsin, the test results are unaffected by pancreatic enzyme replacement therapy.