In order to assess the competing roles of dispositional optimism and neuroticism on reactivity to psychological stress, we selected 50 women (mean age = 18.76 years; SD = 1.9 years) from a screening sample of 150 college students on the basis of having high and low scores in dispositional optimism. In a laboratory, participants provided cardiovascular measures before, during, and after a mentally challenging task, as well as anxiety scores before and after the task. Participants also supplied measures of neuroticism and ratings of task-stressfulness. It was found that neuroticism and not optimism exerted an influence on diastolic blood pressure responses, that neither variable influenced systolic blood pressure responses except in the case of unstable change scores, and that the two variables suppressed each other's influence on anxiety levels (but that neuroticism had a stronger association with anxiety). It was also found that participants' ratings of the stressfulness of the laboratory task, although positively associated with cardiovascular reactivity, did not mediate the relationships among optimism, neuroticism, and cardiovascular measures. The present study confirms the suspicion that optimism is not independent from neuroticism as an index of disease risk.