Epidemiologic studies have revealed that minimal acute-phase changes predict poor prognoses in many conditions and predict disability and mortality in the elderly. These findings have usually been interpreted to indicate that inflammatory processes of some kind play a role in these situations. In fact, a minimal acute-phase response does not necessarily establish the existence of an inflammatory process but may also reflect a variety of noninflammatory states, including obesity, sleep disturbance, depression, chronic fatigue, and low levels of physical activity. I propose that a minimal acute-phase response may also be a marker of biologic aging, a condition known to predispose to poor prognoses and to death.