Acute inflammation results in alterations in both peripheral and central nervous system cytokine levels that together can exert transient but profound alterations in neuroendocrine function. This has been particularly well studied with respect to the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal axes. There is now evidence, particularly in rodents, that an inflammation in the neonatal period can have long-term, sex-specific effects on these neuroendocrine axes that persist into adulthood. There are critical time periods for the establishment of these long-term programming effects, and in adulthood they may be revealed either as alterations in basal functioning or in altered responses to a subsequent inflammatory challenge. These studies highlight the importance of early environmental exposure to pathogens in sculpting adult physiology and behavior.