Given links between interpersonal functioning and health as well as the dearth of truly interpersonal laboratory stressors, we present a live rejection paradigm, the Yale Interpersonal Stressor (YIPS), and examine its effects on mood, eating behavior, blood pressure, and cortisol in two experiments. The YIPS involves one or more interaction(s) between the participant and two same-sex confederates in which the participant is made to feel excluded and isolated. In Experiment 1, 50 female undergraduates were randomly assigned to the YIPS or a control condition. Participants in the YIPS condition experienced greater negative affect and less positive affect than did those in the control condition. Further, restrained eaters ate more following the YIPS than did nonrestrained eaters. In Experiment 2, 25 male and female undergraduates completed the YIPS. The YIPS induced significant increases in tension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) from baseline, while significantly decreasing positive affect. The YIPS appeared particularly relevant for women, resulting in significantly greater increases in cortisol and SBP for women compared to men. The YIPS, then, provides an alternative to traditional, achievement-oriented laboratory stressors and may allow for the identification of individuals most vulnerable to interpersonal stress.