This essay is based on the premise that certain individuals may have a biologically determined propensity to respond to infection that is manifested by the development of disease such as chronic fatigue syndrome; the sequence of events that leads to this response involves the immune system. Biochemical pathways between the immune and nervous system are reviewed, and the role of various products in the systemic circulation, including interleukin-1, pituitary hormone, and catecholamines, is highlighted. This premise could be tested by measuring levels of these substances in carefully selected patients and controls.