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Social isolation is a potent but little understood risk factor for morbidity and mortality, and its negative consequences are most profound among the elderly, the poor, and minorities, some of the fastest growing segments of the U.S. population. A steadily increasing number of people are living alone and are therefore more likely to experience social isolation. We discuss four mechanisms—attractiveness, health behavior, stress, and repair and maintenance—by which perceived social isolation might affect health. Our studies show that neither attractiveness nor health behaviors differ as a function of social isolation, but stress and repair and maintenance do seem to be factors. While socially isolated young adults did not report more frequent everyday stressors, they rated everyday events as more intensely stressful. They were also more likely to report passively coping with stressors, and to show greater vascular resistance, a mechanism of blood pressure control previously associated with passive coping and a risk factor for hypertension. Finally, they exhibited less efficacious repair and maintenance of physiological functioning, including slower wound healing and poorer sleep efficiency.These mechanisms have implications for designing appropriate interventions. We advocate a national health care plan that promotes preventive medicine, recognizes the significance of stress-related disorders, and supports the maintenance of social connections across the life span.