Cardiovascular disease (CVD) is the leading cause of death and disability in older African Americans, and accounts for 40% of the disproportionate risk for mortality observed in African Americans compared to white Americans. The majority of CVD patients experience acute cardiac events, many sudden and unexpected, despite conventional treatment of their disease and associated traditional risk factors. The pathophysiologic basis of these cardiac events is not fully established, but substantial evidence indicates that psychosocial stress and the sympathetic nervous system have adverse effects on both vasomotor function and long-term autonomic balance. Recent advances in the understanding of the pathophysiology of acute cardiac events-specifically, the roles that arterial vasomotor dysfunction and sympathetic nervous system imbalance play in the pathophysiology of such acute events-provide a platform for a new mechanistic investigation of the interplay of psychosocial and environmental stress and CVD. Preliminary evidence demonstrating elevated peripheral vasoconstriction due to stress-mediated sympathetic nervous system response in African Americans further suggests that these mechanisms are particularly relevant in this group.