In both humans and animals certain individuals seek stimuli or situations that are considered stressful and consequently avoided by others. A common feature of such situations is an activation of the hypothalamo-pituitary-adrenal axis leading to secretion of glucocorticoids. Since glucocorticoids have euphoric effects in some individuals and have been shown to potentiate the reinforcing properties of drugs of abuse in animals, we hypothesized that corticosterone secretion during stress-like situations may have reinforcing effects and that a higher sensitivity to the reinforcing effects of glucocorticoids might be a biological basis of sensation seeking. In this report we show that (i) corticosterone has reinforcing properties, as evidenced by the development of intravenous self-administration, (ii) self-administration of corticosterone is observed at plasma levels that are comparable to those induced by stress, and (iii) there are individual differences in corticosterone self-administration, which are related to individual reactivity to novelty and sensitivity to drugs of abuse, behavioral features akin to certain traits of high-sensation seekers. These findings provide insight into the physiological role of glucocorticoids and the biology of sensation seeking and may have clinical implications.