Interactions among the nervous, neuroendocrine, and immune systems render host defenses highly sensitive to autonomic over- or understimulation. Persons with quadriplegia experience decentralization of directly innervated immune tissues and neuroendecrine axis dysregulation, immobilization deconditioning, heightened exposure to immune suppressing xerobiologicals, and psychic and nonpsychic stressors differing from those of nondisabled cohorts. When compared with matched nondisabled controls, young survivors of quadriplegia have reduced CD4:CD8 ratios, suppressed proliferative responses to mitogen challenge, reduced number and cytotoxieity of CD3-CD56+ (NK) cells, and elevation of the soluble IL-2 receptor. Deviations from control values are typically observed in persons with injuries higher than sympathetic outflow, suggesting a cause related to autonomic dysfunction. Cycling exercise performed by persons with quadriplegia using computer-sequenced electrically stimulated contraction of the quadriceps, hamstring, and gluteus muscle groups fails to provoke an archetypical leukocytosis, bill transitionally elevates NK cell number and cytotoxicity lasting one-half hour after exercise. These findings show that the immune system of persons with quadriplegia is selectively responsive to exercise challenge. As opportunistic infections of the urinary tract, lungs, and skin are major causes of morbidity in survivors of quadriplegia, these observations may identify a treatment through which their host defenses can be fortified.