Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test. The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration. 