The circadian clock is a self-sustained time-keeping system which controls behavioral, biochemical and physiological rhythmic processes. In mammals, the cogwheels of this clock are the so-called clock genes which control their own expression via several feedback loops. One of these genes is hPER1, a clock gene which disposes of a glucocorticoid-responsive element and might therefore be influenced by glucocorticoids. In humans, stress is associated with an increase in the glucocorticoid cortisol and is seen as a major factor in the etiology of numerous mental health problems. For this reason, our goal was to investigate the putative cortisol-mediated influence of acute and chronic psychosocial stress on the gene expression of hPER1 as well as hPER2, another related clock gene from the same family. We therefore applied laboratory psychosocial stress to thirty-one healthy men and measured cortisol as well as mRNA levels of hPER1 and hPER2. Our main findings suggest that acute psychosocial stress influences the expression of hPER1 and hPER2 dependent on the subjective experience of chronic stress. We therefore conclude that the reactivity to acute stress on the gene expression level of these two genes differs significantly between subjects with high chronic stress compared to subjects with low chronic stress.