To test the value of dexamethasone acetate for ameliorating acute mountain sickness (AMS), we conducted a double-blind, randomized study that compared the effects of 4 mg of dexamethasone acetate or a placebo (given every six hours for six doses beginning at the time of exposure) at 2700 and 2050 m. Study subjects, who were recruited from health professionals who attended continuing medical education programs at ski resorts in the Rocky Mountains, were classified as having AMS when they reported three or more of the five usual symptoms (headache, insomnia, dyspnea, anorexia, and/or fatigue) on a single day. All symptoms with an intensity of at least grade 2 (moderate) out of 5 were analyzed. At 2700 m, there was a 50% decrease in the mean AMS symptom score in the dexamethasone group (0.94 +/- 1.11 vs 1.84 +/- 1.44 [mean +/- SD]) and the incidence of AMS was 20% of that in the control group (3/38 vs 14/35). At 2050 m, there was no difference between dexamethasone and a placebo in the mean AMS symptom score (1.52 +/- 1.50 vs 1.24 +/- 1.33) and the incidence of AMS (5/25 vs 4/25). Dexamethasone ameliorates the usual symptoms of AMS at 2700 m but not at 2050 m.