Age-related changes in Kupffer cell numbers and function may have important implications for systemic immune responses and hepatic function. We compared numbers of Kupffer cells in the hepatic sinusoids and phagocytic function of Kupffer cells in isolated perfused livers of young, middle-aged, and old rats. On light microscopy, the number of Kupffer cells per 29,500 mum(2) field increased with increasing age (young 2.0 +/- 0.2, n = 8; middle aged 3.3 +/- 0.3, n = 7; old 5.5 +/- 0.6, n = 7). After a single pass through the liver, the ratio of the fractional recovery of 500 nm polystyrene microspheres to that of sucrose decreased significantly with increasing age: young rats, 89 +/- 35% (n = 7); middle-aged rats, 58 +/- 18% (n = 9); and old rats, 49 +/- 24% (n = 10), suggesting increased Kupffer cell phagocytic activity. In old age, increased Kupffer cell numbers and activity were observed in the basal state.