Loss of basal forebrain cholinergic neurons (BFCN) occurs in many age-related neurological diseases. Although age is the common risk factor in these disorders, no consistent age-related changes have been reported in the human BFCN. We investigated age-related alterations in choline acetyltransferase (ChAT), low-affinity nerve growth factor receptor (p75LNGFR) and calbindin-D28k (CalBP) immunoreactivity in the human BFCN. No significant age-related changes were observed in ChAT or p75LNGFR immunoreactivity. By contrast, normal aging was accompanied by a selective, substantial and significant loss of CalBP immunoreactivity from the BFCN. Other CalBP-positive neurons were unchanged. Loss of the calcium buffering capacity conferred by CalBP may leave the BFCN vulnerable to damage in neurodegenerative disorders.