Lavaged alveolar macrophages of mice were examined by light and electron microscopy primarily using cytochemical reactions for lysosomal enzymes. Among several methods tried, the Reed and Bennett procedure for N-acetyl-β-glucosaminidase (J. Histochem. Cytochem., 23:752–757 (1975)) was preferred for use in smears and the Gomori acid phosphatase method for ultrastructural study. Prior to examination, some mice were exposed to an aerosol of finely divided iron oxide for 1–3 hours at particle concentrations of 80–290 mg/m3, others breathing clean air provided macrophages for comparison. Both exposed and unexposed macrophage populations were composed of a similar range of subtypes differing in cytological appearance and enzymic activity. The exposed populations tended to contain a higher proportion of strongly reactive cells, notably of a kind possessing many elongate lysosomes; consequently, it appeared that many cells in these populations were substantially engaged in synthesizing lysosomes. Based on this material, the cycle of production was reconstructed. This is divisible into five natural stages, defined primarily by the intracellular distribution of lysosomal enzyme activity and to a lesser extent by other cytological criteria. Commencing in immature cells, where the predominant localization of acid phosphatase activity in the Golgi apparatus and a few rounded lysosomes (Stage 1), the cycle continues through a period dominated by extensive growth of the granular endoplasmic reticulum (Stage 2). With the appearance of a crop of elongate or lumbricoid lysosomes, the predominate locus of acid phosphatase activity shifts from the Golgi apparatus to these bodies (Stage 3). Thereafter, they often are seen together with an increased number of large rounded lysosomes (Stage 4), but in other cells only the latter are to be found (Stage 5). This lysosomal cycle operates in cells showing other signs of an aroused metabolism, and it appears not to be closely tied to the mitotic cycle. The nascent lumbricoid lysosomes seem to be formed at some distance from the Golgi apparatus, wheras the lysosomes produced by more quiescent cells often lie in close relationship to that organelle.