The immune system is influenced by central nervous system processes that are shaped by social and psychological factors. Considerations of social factors, intrapersonal process, and autonomic psychophysiology therefore may contribute to a fuller understanding of both immune and brain function. Research reviewed here (a) examines the socioemotional factors that contribute to, or moderate, responses to brief and chronic stressors, (b) determines whether or not stable individual differences in heart rate reactivity predict neuroendocrine and immune responses to a brief psychological stressor and to an influenza virus vaccine, and (c) investigates the autonomic origins of individual differences in low and high heart rate reactivity and their relationship to neuroendocrine and immune responses to chronic and acute stressors. Among our findings are: (a) acute psychological stressors activate the sympathetic adrenomedullary system across individuals and affect immune function; and (b) individuals characterized by high sympathetic cardiac reactivity to acute psychological stressors also show a relative activation of the hypothalamic pituitary adrenocortical system and altered immune function.