Gene knockout technologies have been used to elevate the mouse as a model species. However, little work has examined age and strain differences in the mouse olfactory system. The present study compared the olfactory bulbs of mature (6 month) and aged (24 month) males of BALB/cBy, C57BL/6J, and DBA/2 strains. Volumes of the glomerular (GLM), external plexiform (EPL), and mitral/granule cell (MIG) layers varied little from strain to strain. Volume measurements increased with age even when corrected for body weight differences. Two nonoverlapping interneuron populations were examined with immunohistochemistry. Staining for the calcium binding protein calretinin varied little between strains, but age-related increases in staining were seen in EPL of C57BL/6J mice. Typical patterns of tyrosine hydroxylase immunoreactivity were observed in all subjects except for old DBA/2 mice, which evidenced considerable staining in submitral areas. Age-related increases were observed in BALB/cBy and DBA/2 mice but not in the C57BL/6J strain. Glial fibrillary acidic protein staining was similar in old BALB/cBy and DBA/2 mice, with astrocytes in all layers of the bulb, but more concentrated in the MIG. However, C57BL/6J tissue revealed very large astrocytes relatively evenly distributed in all layers. Cell proliferation dropped dramatically with age. Labeled cells could still be observed along the lateral ventricles, but very few were observed within the rostral migratory stream or subventricular zone. Although TUNEL labeling revealed many apoptotic figures in the granule cell layer of young subjects, almost no staining was seen in aged mice.