This study compared calbindin D-28k immunoreactivity in the medial nucleus of the trapezoid body (MNTB) in young (3-4 month old) and old (24-26 month old) CBA/CaJ mice, and young (3-4 month old), middle-aged (6.5-8.5 month old), and old (24-29 month old) C57BL/6 mice. C57BL/6 mice exhibit progressively more severe peripheral (sensorineural) hearing loss between 4 and 12 months of age, whereas CBA/CaJ mice show little change in peripheral sensitivity until very late in life. We obtained auditory brainstem response audiograms on all subject mice. Old CBA mice were selected for study whose audiograms matched those of young CBA and C57 controls. Middle-aged C57 mice showed elevated thresholds indicative of peripheral degeneration. Brain sections were reacted with anti-calbindin D-28k (CB). Staining patterns in Nissl and anti-CB material were characterized and cells were counted. We found no significant change in the number of CB+ cells or the total number of cells in the MNTB of old CBA mice compared to young controls. However, the mean number of CB+ cells decreased by 11% in middle-aged, and by 14.8% in old C57 mice. Since the decline in C57 mice was significant by 6.5-8.5 months of age, the decrease could be the consequence of a loss of input from the cochlear nucleus where cell numbers are known to decline by this age in this strain. The total number of neurons in MNTB assessed from Nissl material showed a more modest 7.1% decline with age in C57 mice, implying that the greater loss of CB immunoreactive cells with age cannot be completely attributed to a reduction in the total number of cells.