Intestinal malabsorption of nutrients may be a critical factor in aging. For this reason, we investigated the nutrient absorption in mice of different ages of the life span, representing growth (3 mo), young adult (12 mo), mature (24 mo), old (30 mo), and very old (33-36 mo) periods. The everted sac technique was used to study the transepithelial transport of D-glucose, 3-O-methyl-D-glucose (3MG), and L-tyrosine. There was a 32% increase in the rate of D-glucose transepithelial transport during growth followed by a 55% decrease in the old mouse, and the same pattern occurred with 3MG, a nonmetabolized glucose derivative. However, L-tyrosine transepithelial transport was not impaired until the mouse reached the very old, 33-36 mo period. Also, the rate of D-glucose metabolism measured by lactate production in the very old mouse was only 45% of the mature mouse value. In addition, these transepithelial transport changes were accompanied by decreases in the number and the height of villi. The results indicate that intestinal transepithelial transport and the surface area for absorption decrease in aging.