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Sick-building syndrome is an illness characterized by fatigue, headache, and upper-respiratory complaints. It is usually associated with modern office buildings, structures with an impervious outer shell and inoperable windows. Poor air quality, specific pollutants, and inadequate ventilation are considered common causes. The ability to smell faint odors requires air that is free of contamination. Human evolutionary ancestors depended on odors for survival. Even the slightest increase in the ability to smell a predator conveyed a distinct, immediate survival advantage. Conversely, an enormous survival advantage would also accrue to the animal that sought protection or avoided activity when this vital olfactory information was unavailable. Such would be the case with fire on the savannah. The foraging, olfactory dependent animal, unable to smell predators because of contaminated air, would be quickly snatched by a keen-sighted carnivore. There exist, however, well-described reflexes from the nose mediated through the trigeminal nerve that discourage activity when these free nerve endings are irritated. This mechanism may serve as a defense against predation. In adulterated atmosphere the animal, subdued by these reflexes, would be less likely to venture forth and, therefore, less vulnerable to predators. Similar reflexes may persist in humans, activated by poor air quality, air ill-suited for the dissemination of odors. I suggest that the human perception of these inhibitory reflexes is the feeling of fatigue associated with the sick building syndrome.