Based on previous findings in men, the hypothesis that hostility would be associated with blunted responsiveness of cardiovascular beta-adrenergic receptors was tested in a study sample of middle-aged women. The roles of the sympathetic nervous system and of social support in this putative relationship were also evaluated. Subjects were 80 healthy women (n = 23 African American; n = 57 white), aged 47 to 55 years. Hostility was assessed using the Cook-Medley Hostility Scale and social support was assessed with the Brief Social Support Questionnaire. Intravenous isoproterenol challenge was used to evaluate cardiac and vascular beta-adrenergic receptor responsiveness. Twenty-four-hour urinary catecholamine excretion was used to index sympathetic nervous system activity. Hostility was related to blunted cardiac (R = 0.33, p <.01) and vascular (R = 0.23, p <.05) beta-adrenergic receptor responsiveness in simple correlation analysis and in hierarchical regression analyses controlling for race, menopausal status, weight, and resting heart rate. Low social support was also related to blunted beta-adrenergic receptor responsiveness (R = 0.3, p <.01). Twenty-four-hour norepinephrine excretion was related both to hostility (R = 0.32, p <.01) and to cardiac (R = 0.25, p <.05) and vascular (R = 0.24, p <.05) beta-adrenergic receptor responsiveness. These observations replicate and extend previous findings in men by demonstrating that higher levels of hostility and low levels of social support are associated with blunted beta-adrenergic receptor responsiveness in middle-aged women. They also suggest that heightened sympathetic nervous system activity associated with hostility may contribute to beta-adrenergic receptor blunting. Because blunted beta-adrenergic receptor sensitivity is a characteristic feature of a broad range of cardiovascular diseases, these findings may reflect an early preclinical manifestation of pathophysiology accompanying hostility and low social support.