The development of the exocrine pancreas has been determined quantitatively in 31 infants with cystic fibrosis (CF) both with and without meconium ileus and in 29 control infants. In the normal pancreas, the ratio of acinar to connective tissue volume is 0.5 at 32 weeks postconceptional age (PCA) and increases linearly to 2.0 at 52 weeks PGA. In cystic fibrosis infants, with or without meconium ileus, the ration is 0.5 at 35 weeks PCA anddecreases linearly to 0.3 at 52 weeks PCA. The volume of acinar and duct lumens is greater in CF than control infants but is independent of age or acinar volume. The development of the exocrine pancreas in infants with CF with and without meconium ileus diverges from the normal pattern: There is consistent lack of exocrine tissue before or a full-term birth, which persists throghout the age range of this study. CF infants above 42 weeks PCA can be discriminated from controls on the basis of the quantitative assessment of acinar volume.