BACKGROUND & AIMS: It is suggested that stress particularly in subjects with high cognitive reactivity (CR), a psychological vulnerability marker of depression, may increase or even induce serotonergic vulnerability, which in turn may lead to reduced serotonin (5-HT) function, decreased stress coping and an increased risk to develop depressive symptoms. The aim of the present study was to investigate the beneficial effects of 5-HT augmentation through a tryptophan-rich hydrolyzed protein (HP) on mood and stress coping in subjects with high and low CR. We hypothesized that subjects with high CR are more responsive to the beneficial effects of HP than subjects with low CR particularly after acute stress exposure. METHODS: In a double-blind, crossover study, participants' mood and cortisol was assessed before and after acute stress exposure either following intake of HP or a standard casein protein (CP) as control condition. RESULTS: HP significantly increased positive mood in all subjects and dampened the cortisol response to acute stress. No differences were found between high and low CR subjects. CONCLUSIONS: To conclude, because dietary treatment with HP has beneficial effects on mood and physiological stress coping in both high and low CR subjects, HP may be a good dietary method for augmenting brain TRP and 5-HT and thus 5-HT linked stress resilience.