This study examined the effects of dexamethasone and exposure to high terrestrial altitude on cognitive performance, affect, and personality. Cognitive performance was evaluated by five cognitive tasks, affect was evaluated by the Clyde Mood Scale and the Multiple Affect Adjective Check List, and personality was examined using the Minnesota Multiphasic Personality Inventory. Sixteen healthy young men received either dexamethasone (4 mg every 6 h) (n = 7) or placebo (n = 9) for 34 h prior to and 52 h after ascent to 4,300 m. Subjects treated with dexamethasone correctly performed more computer interaction and addition problems than did placebo-treated subjects. They also were less sleepy, dizzy, depressed, and anxious than placebo-treated subjects at altitude. No adverse effects on cognitive performance, affect, or personality were noted after dexamethasone was discontinued on the third day at altitude. Results indicate that dexamethasone at the present dose positively influences cognitive performance and mood states at altitude, but has no residual effect on personality.