Abstract: Excessive stress loadings in daily life are believed to play a role in the development of affective disorders. Our recent finding of enhanced neuroendocrine activation during stress of hypoglycemia after repeated antidepressant treatment in healthy men supports the hypothesis that the clinical effects of antidepressant treatment may be partly due to the adjustment of the stress response, which was reported to be blunted in depressive patients. The present double-blind placebo-controlled study investigated the effects of 6 days of treatment with the antidepressants citalopram or tianeptine on neuroendocrine activation during mental stress. Blood pressure, heart rate, and salivary cortisol values were measured. The stress procedure, lasting 17 min, consisted of a short intelligence test followed by the Stroop word-color interference test. Citalopram treatment was associated with a significant enhancement of stress-related increase in systolic and diastolic blood pressure. No differences were observed in the heart rates and salivary cortisol. Comparisons based on cluster analysis revealed that subjects with poor performance in the Stroop test displayed a significantly lower rise of systolic and diastolic blood pressure values after the stress procedure and lower prestress cortisol levels in saliva when compared to the good performing subjects. Our findings show that antidepressant treatment can enhance the neuroendocrine response also during mental stress, and suggest that mental performance during stress is related to the pattern of cardiovascular and adrenocortical activation.