We have analyzed both free L- and D-serine in frontal cortex of normal and Alzheimer human brain by high-performance liquid chromatography (HPLC). There was no significant difference between the two brains. In normal brain, L- and D-serine concentrations were 666 +/- 222 and 66 +/- 41 nmol/g of wet tissue, respectively, and the ratio of D-isomer to L-isomer (D/L) was 0.099 +/- 0.031. In Alzheimer brain, the concentrations were 750 +/- 150 and 66 +/- 40 nmol/g, respectively, and the D/L ratio was 0.086 +/- 0.040. Thus, it was shown that the free D-serine concentration in the Alzheimer brain was comparable to that in the normal brain.