GOAL: To compare, during strong acid inhibition with omeprazole, the effect of 2 different doses of an enteric-coated pancreatic enzyme preparation on fecal fat excretion and abdominal symptoms in patients with exocrine insufficiency due to chronic pancreatitis (CP). BACKGROUND: Treatment with pancreatic enzymes reduces fecal fat excretion in patients with CP but is rather unsuccessful due to irreversible lipase inactivation at pH below 4. STUDY: Sixteen patients with CP (3 women, 13 men; age 53+/-3 y) participated in this randomized double blind 2-way cross over study. Fecal fat excretion and fat intake were measured and abdominal symptoms (visual analog scales) were scored during a 2 weeks control period, during omeprazole 60 mg+pancreatic enzymes 10,000 Federation Internationale Pharmaceutique IU lipase tid (treatment A) for 2 weeks and during omeprazole 60 mg+pancreatic enzymes, 20,000 Federation Internationale Pharmaceutique IU lipase tid (treatment B) for 2 weeks. RESULTS: During acid inhibition with enzyme supplementation fecal fat excretion was significantly (P<0.01) reduced compared with control: 18+/-7 and 18+/-5 g/24 h versus 36+/-8 g/24 h for treatment A, B, and control, respectively. Abdominal symptom score and general well being improved significantly (P<0.05) during treatments A and B versus control. No differences in fat excretion or symptoms scores between treatments A and B were observed. CONCLUSIONS: During strong acid inhibition, lower than recommended oral doses of pancreatic enzymes are therapeutically effective with respect to fat absorption and symptom reduction.