Histochemical methods were used to study the development of representative enzymes associated with lysosomal activity in sections of lung from late fetal, neonatal, and adult rats. Staining for β-glucuronidase and acid phosphatase was present in the fetus and afterbirth, and the number and intensity of reactive cells increased to adult levels by the seventh to tenth day of life. Reactions for β-galactosidase were not found in newborn animals, but moderate staining was seen by the fourteenth day. In contrast to these lysosomal enzymes, intense cytochrome oxidase staining was found in all specimens, and no age-dependent changes were seen. Acid phosphatase activity was present in nearly all cells in the adult lung, but the indolyl reactions for the glycosidases were localized to single cells. In spite of this resolution, it was not possible to identify with certainty many of the reactive cells. Most appeared to be type II epithelial cells. Alveolar macrophages were usually reactive, but relatively few such cells were found, especially in the neonatal specimens. The results of this and other studies indicate that these cells have many common metabolic pathways. Other data, however, suggest a dissimilar origin and function of type II cells and macrophages.