To evaluate claims that enteric-coated pancreatic enzyme preparations are more effective than conventional digestants in managing malabsorption in cystic fibrosis (CF), we conducted a trial comparing the efficacy of pancrealipase (enzyme supplement containing lipase, amylase, and protease) in the form of pH-sensitive microspheres (Pancrease) with that in the form of encapsulated enzyme powder (Cotazym). Ten boys with CF received equivalent dosages in a controlled, double-blind fashion using a random sequence of capsule administration with crossover and "washout" periods. Patients experienced significantly enhanced nitrogen and fat absorption while receiving either enzyme when compared with placebo. The enteric-coated product promoted significantly improved fat absorption as compared with the conventional enzyme capsule. Both enzyme preparations caused significantly improved protein absorption as compared with placebo, but there as no significant difference between the two products in the degree of effect on azotorrhea.