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Laboratory investigations of cardiovascular reactivity to mental stress often ignore concomitant differences in cognitive, affective, and behavioral responses that are commonly observed among study participants. To provide a more systematic laboratory methodology to examine relations among cardiovascular, behavioral, and self-report measures of cognitive and affective responses to stress, we developed and tested a social confrontation procedure involving standardized interactions during two scenes. Results of three investigations are presented to illustrate the utility of the social confrontation procedure. In the first two studies, this multidimensional assessment strategy produced results which may foster research projects that bridge separate areas of psychological inquiry. In one application, persons with hypertensive parents, in contrast to persons with normotensive parents, exhibited characteristic negative behavioral responses during both interactions as well as the more commonly-observed exaggerated blood pressure reactions. In the other study, students from less functional families (regarding cohesion and adaptability) were shown to exhibit exaggerated blood pressure reactions in addition to their commonly-reported negative cognitive and behavioral coping styles. Finally, a third study examined how a simple instructional set regarding the expression or suppression of anger influenced participants' responses. Significant differences were observed across response domains, with anger expression resulting in a more intense response than anger suppression. In sum, the social confrontation procedure represents an important methodological development for exploring the relation between response domains, the relation between cardiovascular response to stress and psychosocial risk for cardiovascular disease, and the physiological and behavioral distinction between anger expression and anger suppression.