Previous research has shown that uncertainty constitutes a powerful stressor (e.g. Monat, Averill, & Lazarus, 1972; Zakowski, 1995), although individual differences in reactions to uncertainty have not been investigated adequately. The Uncertainty Response-Emotional factor from the Uncertainty Response Scale (URS—Greco & Roger, 2001) measures individual differences in the extent to which uncertainty is perceived as stressful. This paper addresses the relationship between uncertainty and health by means of an experiment in which physiological arousal was measured during a period of experimentally-induced uncertainty. Results showed that Uncertainty Response-Emotional predicted increases in both systolic and diastolic blood pressure during a period of anticipation prior to the occurrence of a possible threat of unknown intensity.