Brain weight, total solids, protein, and major lipids have been determined in 83 female and 101 male brains from subjects 20-100 years of age. The brain weight began to diminish at 20 years of age. The brain weight at 20 years for females: 1,368 +/- 26 and for males 1,632 +/- 27 g diminished at 100 years for females to 1,100 +/- 25 and for males to 1,266 +/- 25 g, a decrease of 20% for female and 22% for male brains. The decrease in dry solids was larger during the same period, 36% for females and males. Proteins decreased by 39% in females and 37% in males. Phospholipids decreased by 42% in females and 43% in males, cholesterol by 47% and 53%, cerebroside by 46% and 58%, sulfatide by 46% and 49% and gangliosides by 28% and 30%, respectively. There is, thus, a significantly larger loss of myelin lipids than of gangliosides-the biochemical marker for neuronal membranes. The loss of myelin lipids was particularly large in female brain after 70 years of age, while the loss in male brain was linear as early as from 20 years of age.