In the present study we investigated the effects of cortisol administration on EEG activity in eight healthy volunteers. We administered 35 mg of cortisol in a within-subjects double-blind placebo-controlled design. Cortisol administration caused a global decrease in cortical activity except for an increase frontally at the left, resulting in a significant change in frontal asymmetry. This pattern of results is almost the exact mirror image of one of our previous studies. Comparing subjective activation measures from the present and previous study showed that activation was substantially higher in the present study that was performed in formal testing conditions involving venipuncture, compared to the previous EEG study that was performed in non-formal testing conditions. However, the direction of the present cortisolinduced change in frontal activity asymmetry is consistent with the cortisolinduced change in asymmetric rotation behavior that we recently reported in similar testing conditions. We also found indications that, in contrast to the effects on the EEG measures, effects of cortisol administration on subjective anxiety and plasma oxytocin levels may be sex-dependent. These results are preliminary because of the post-hoc nature and the small number of subjects in the present study. However, they are in line with recent findings by others, suggesting that the effects of cortisol on cortical activity and subjective activation are state dependent and are influenced by testing conditions. © 2006 Elsevier Ireland Ltd. All rights reserved.Keywords: Cortisol; EEG; Frontal asymmetry; Venipuncture stress; Testing conditions; Alpha powerThe hormone cortisol has a wide range of physiological functions, including the mobilization of resources and stressprotective down-regulation of other physiological systems [3]. Effects of cortisol are context-and state-dependent [3]. Reuter studied the effects of cortisol administration on self-reported mood and activation under stress (violent film) and nonstress (neutral film) conditions [13]. Reuter summarized his results as indicating an adaptive activating effect of cortisol in conditions in which there is a loss of activity due to lack of stimulation since it prevents a further decrease in activity, whereas in stress conditions the organism is protected from overactivation. Indeed, recently it was found that acute cortisol treatment attenuated increases in fear in response to phobia-related stimuli in both a group of subjects with social phobia and a group with spi- * Correspondence to: NeuroInformatics Center, University of Oregon, OR 97403, USA. Tel.: +1 541 6862903; fax: +1 541 6877963.E-mail address: mtops@darkwing.uoregon.edu (M. Tops).der phobia [15]. Similarly, mere testing conditions modulate the effects of cortisol on memory retrieval. In line with observations in rats, Kuhlman and Wolf observed that cortisol administration impaired memory retrieval in a formal testing condition, while it had no impact on retrieval in a very relaxed non-formal testing condi...