Studies in several species have demonstrated that an adverse early environment can influence the development of the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis. The autonomic nervous system and HPA axis are key components of the neuroendocrine response to stress and many of these animal models show altered biological responses to stress. Recent research now suggests that these processes operate in humans. An adverse early environment, as evidenced by reduced birth or infant weight, is associated with enhanced autonomic and HPA responses to experimental psychological stress. However, there appear to be marked sex differences in the mechanisms involved. Epidemiological studies demonstrate that physiological changes in these neuroendocrine systems may predispose to cardiovascular disease through their influence on risk factors such as plasma glucose and lipid concentrations and blood pressure. Thus the combination of enhanced stress susceptibility and the psychosocial stressors to which people are exposed may be an important component of the disease risk in human populations.