Pancreatic enzymes (PE) are prepared as pH-sensitive enteric coated microspheres [Pancrease, Alipase in France (P)], to prevent gastric inactivation of orally administered enzymes. The efficacy and tolerability of P were compared to those of Eurobiol (E) (PE lacking enteric coating) in patients with exocrine pancreatic insufficiency (PI) via an open crossover study conducted at 16 centers in France. Pancreatic insufficiency was diagnosed in patients with signs of chronic pancreatitis who showed steatorrhea (fecal fat excretion greater than 8.0 g/24 h). The dosage of P was 9 capsules/d and that of E, 3 vials/d. Stools were collected for 3 consecutive days at each of the following periods: after 10 d without any PE, and after 21 d of P and E administration. Results were analyzed statistically by the method of Hills and Armitage. Chronic pancreatitis was alcohol-induced in 33 of 35 patients (94%) who entered the study. The group that received P before E (n = 20) was comparable to the group that received E before P (n = 15) in patient and disease characteristics. Eight of 35 patients failed to complete the study for the following reasons: adverse reactions 2 cases, lost to followup 4 cases, dropped out of study 2 cases. The degree of steatorrhea was similar after P and E. However, symptomatic improvement was noted far more frequently with P than with E. Moreover, patients preferred P to E because of drug taste (p less than 10(-4] and ease of drug administration (p less than 10(-3). Drug safety was comparable in the two groups of patients.