The transition to geriatric status occurs at around 20 years of age in monkeys after which there is typically a decline in immune responses. However, the loss in immune vigor may be quite dissociated from chronological age in some of these long-lived animals. The degree to which natural killer (NK) cell activity is sustained in aged monkeys has proven to be a valuable prognostic of ultimate health and longevity. Another useful biomarker of cellular aging in the monkey is interleukin-6 (IL-6) release. For example, when endothelial cell cultures were generated from cerebral blood vessels, those derived from aged donors produced significantly more IL-6 in response to IL-1, LPS, and hypoxia. Despite this evidence of intrinsic aging, we have found that immune responses in old animals are quite responsive to contemporaneous conditions, including changes in housing or the first onset of illness. Indeed, these changes, especially the pathological processes associated with disease, may promote many age-related immune alterations at the end of the life span.