The administration of purified cytokines to animals has been shown to cause a number of effects on the brain, including neuroendocrine effects, behavioral effects and alterations of brain biogenic amines. The best-documented effects are the activation by interleukin-1 (IL-1) of the hypothalamo-pituitary-adrenocortical (HPA) axis, and cerebral norepinephrine and indolamine metabolism. IL-6 and TNF alpha may also activate the HPA axis, and IL-6 activates cerebral indolamines. There are a few reports of other responses, but for proper evaluation it is important that studies be conducted using purified homologous cytokines, free of endotoxin contamination. The effects of the cytokines on the brain are believed to be a major mechanism by which infections and immune challenges signal the brain and activate endocrine and behavioral responses. The noradrenergic responses to IL-1 may be related to HPA activation, but the significance of the indolaminergic responses is unknown.