Elderly people contract more gram-negative infections than does the younger population and, thus, are exposed to larger amounts of bacterial endotoxins. The differential effects of bacterial lipopolysaccharides (LPS) in aging have been investigated here. LPS have increased toxicity for aged mice (12 and 24 months) compared to that in 2-month-old mice in that two-thirds of both 24-month-old Balb/c and C57Bl/6 male mice were killed by an intravenous dose of 50 microgram of LPS. Body temperatures were also affected by aging. Both C57Bl/6 and Balb/c mice showed a maximum body temperature at 12 months of age; 24-month-old mice had mean body temperatures of at least 2 C less than 12-month-old animals. LPS induced hypothermia in young mice as described by others, but in 24-month-old mice there was a marked hyperthermia following LPS injection. Increased sensitivity to LPS with age may result from differences in the effects of LPS on target cells or differences in responsiveness to secondary mediators. In addition, LPS have profound effects on the immune system which may be changed with age.