One function of the nonciliated (Clara) cells of bronchiolar epithelium is to synthesize, store, and release small-molecular-mass (6-12 kDa) secretory proteins or Clara cell secretory protein (CCSP). This study compares the emergence of this secretory function during Clara cell differentiation in rabbits and rats. Lungs of fetal and postnatal animals were evaluated by ultrastructural morphometry and immunohistochemistry. Secretory granules were rarely seen in perinatal animals and increased to adult levels of abundance earlier in rats (1 wk postnatal) than in rabbits (3-4 wk). In contrast, rough endoplasmic reticulum was abundant in perinatal animals and decreased with age. Antibodies raised against CCSP revealed little CCSP in fetal animals; however, after birth CCSP increased to adult levels earlier in rats (1 wk postnatal) than in rabbits (3 wk). We conclude that the maturation of Clara cell secretory function 1) occurs postnatally, 2) involves a decrease in biosynthetic organelles, 3) shows close association between CCSP expression and secretory granule abundance, and 4) varies by species in timing and cellular abundance of biosynthetic machinery.