The aim of this study was to investigate the influence of trait anxiety and menstrual cycle phase on neuroendocrine activation during combined mental and physical stress procedure in 40 healthy female subjects. Women at the upper (anxious) and lower (nonanxious) limits of the normal range of a trait anxiety scale were exposed to the stress procedure consisting of a mental component (Stroop test) and handgrip exercise. Salivary cortisol levels, cardiovascular parameters, and cognitive performance in the Stroop test were evaluated. Stress-induced cortisol levels and the rise in systolic blood pressure were affected by both trait anxiety and menstrual cycle phase. The stress model used induced a significant cortisol elevation only in anxious women in the follicular phase. This group of women also exhibited greater increases in systolic blood pressure in response to handgrip exercise as compared to anxious ones in the luteal phase and to nonanxious women in either phase. In nonanxious women, stress-induced cortisol levels positively correlated with cognitive performance. In contrast, a negative correlation trend was observed in anxious subjects. Thus, in subjects with low but not high trait anxiety, enhanced cortisol concentrations seem to be associated with better cognitive performance. The results suggest that women with high trait anxiety exhibit greater cardiovascular and hormonal sensitivity to stress stimuli during the follicular phase.