Glutathione and "total" carnitine (i.e., free carnitine plus acid-soluble carnitine esters) were measured in an affected (superior frontal gyrus; SFG) and unaffected (cerebellum: CBL) region of Alzheimer disease (AD) and control brains. Average glutathione content in AD SFG (n = 13) and AD CBL (n = 7) (7.9 +/- 2.1 and 11.9 +/- 4.0 nmol/mg protein, respectively (mean +/- S.D.)) was similar to that in control SFG (n = 13) and CBL (n = 6) (7.7 +/- 2.0 and 11.6 +/- 2.6 nmol/mg protein, respectively). However, glutathione increased significantly with age in AD brain (p = 0.003) but not in control brain. Average total carnitine in AD SFG (84 +/- 47 pmol/mg protein; n = 10) and AD CBL (108 +/- 86 pmol/mg protein; n = 7) was not significantly different from that in the corresponding regions of control brain (148 +/- 97 (n = 10) and 144 +/- 107 (n = 6) pmol/mg protein, respectively). However, a significant decline of total carnitine with age in both regions was noted for AD brain, but not for control brain. Carnitine acetyltransferase activity in the AD SFG (n = 13) was not significantly different from that of control SFG (n = 13) (1.83 +/- 1.05 and 2.04 +/- 0.82 nmol/min/mg protein, respectively). However, carnitine acetyltransferase activity of AD CBL (n = 7) was significantly lower than that of control CBL (n = 6) (1.33 +/- 0.88 versus 2.26 +/- 0.66 nmol/min/mg protein; p = 0.05).