The purpose of the present study was to investigate basic methodological issues related to the usage of an examination stress protocol in studies of psychoneuroendocrinology. In the present study, 57 undergraduate students served as participants. All subjects provided salivary samples and completed psychological inventories during a low examination stress period and again during a high examination stress period. Salivary samples were analyzed for cortisol. Three major findings were observed. First, the examination stress protocol proved to be an effective trigger of elevations in both psychological measures of stress and in cortisol levels. Second, sex differences were observed in cortisol levels, such that males showed an elevation in cortisol during the high examination stress session whereas females did not. Finally, no significant correlations were observed between elevations in psychological measures of stress and elevations in cortisol levels. These findings suggest that the examination stress protocol used in the present study effectively elevated both psychological stress and cortisol levels. Furthermore, these findings suggest that there are biological differences in how males and females respond to stress. Finally, no evidence was found to suggest a relationship between psychological and hormonal levels of stress. Together, these findings suggest the need to better define and consider the implications of both the specific measures of stress being used and individual differences in the subject samples in psychoendocrine studies.