A new enteric-coated pancreatic enzyme preparation (microspheres) was compared with traditional enzyme tablets in six subjects with severe exocrine pancreatic insufficiency. The microspheres were found to be as effective as traditional enzyme supplements. In most patients in balance studies, the lowest fecal fat values were obtained with microsphere therapy in spite of a smaller amount of lipase administered (6015 vs 10,800-43,200 lipase units per meal). In contrast to enteric-coated tablets, microspheres can be recommended in the treatment of pancreatic steatorrhea.