In two studies, saliva cortisol responses to the psychological stress of public speaking and mental arithmetic were investigated in women using oral contraceptives (OC; n = 28) and in control women (n = 29). While no significant differences in baseline levels were observed, altered adrenocortical responses were found in OC users. These women showed significantly attenuated cortisol responses to the experimental stressor in both studies, with peak cortisol levels only slightly elevated above baseline levels. These differences could not be attributed to affective responses as indicated in ratings on visual analogue scales assessing subjective stress responses (Study 2). A comparison between control women and men (n = 19) again revealed the previously reported result of larger cortisol responses to psychological stress in males. We conclude that the use of OC may interfere with the adrenocortical response to psychological stress and should therefore be viewed as an important intervening variable. While it appears that differences at a supra-adrenal site is responsible for the observed cortisol hyporesponsiveness in OC users, the physiological mechanisms remain to be elucidated.