The present double-blind cross-over study aimed to discriminate effects of dexamethasone (DEX) and cortisol (CORT) on mood in ten healthy men. DEX is assumed to predominantly activate glucocorticoid receptors (GR) whereas CORT binds central nervous mineralocorticoid receptors (MR) as well as GR. Mood was assessed by an extensive adjective checklist (Eigenschaftswoerterliste) every morning during two 7-day experimental periods. During one of these periods, subjects were subchronically treated with placebo, during the other they received DEX (4 mg/day). On days 5 and 7 of these periods, (in a balanced manner) either placebo or CORT (10 mg/h) was infused during the night (9 h) before mood assessment. DEX, acutely, enhanced activation, concentration, and arousal (p < .05). During prolonged DEX administration, the energizing effect of the glucocorticoid decreased, but emotional arousability and negative feelings (anger, sadness) were significantly enhanced. CORT administered during prolonged DEX treatment, counteracted these negative feelings, and enhanced scores on a dimension of "high spirits". Sole administration of CORT also enhanced "high spirits" (p < .05) and, like DEX, activation and concentration (p < .05). Results suggest GR to mediate an energizing effect and, with prolonged activation, a dysphoric influence on mood. Predominant activation of MR appears to mediate changes towards euphoric mood.