We investigated the relationship between apolipoprotein E (apoE) polymorphism and cardiovascular responses to experimentally induced mental stress. Mental stress was induced in 28 healthy 16-year-old boys with a series of stressors (e.g., mental arithmetic, Stroop Color-Word Interference Test). Heart rate (HR), finger blood volume, and skin conductance level were recorded continuously during the task performance. We found that boys with apoE3/2 or apoE3/3 showed marginally significantly greater HR reactivity and significantly greater task levels of HR and HR variability (HRV) during the mental stress than subjects with apoE4/2, apoE4/3, or apoE4/4. In addition, E4/2, E4/3, and E4/4 subjects manifested a distinct stress-related decrease in HRV relative to baseline values while E3/2 and E3/3 subjects showed a slight increase. The results suggests that apoE polymorphism is associated with cardiovascular responsivity to mental stress in adolescent boys.