We wished to determine in a field study the effectiveness of dexamethasone for prevention and treatment of acute mountain sickness (AMS). Prevention Trial: We transported 15 subjects from sea level to 4,400 m (PB = 400 mm Hg) on Denali (Mt. McKinley) by means of a 1-h helicopter flight. In a randomized, double-blind fashion we gave eight subjects a placebo and seven subjects 2 mg dexamethasone orally every 6 h, starting 1 h before take-off. The entire placebo group and five of the dexamethasone group developed AMS within 5 h, and became progressively more ill until 12 h when the trial was terminated. We concluded that 2 mg of dexamethasone every 6 h did not prevent AMS in active soldiers rapidly transported to high altitude. Treatment Trial: We treated 11 of those with moderate to severe AMS (symptom score 4.5 +/- 0.7, range 3 to 11) with 4 mg of dexamethasone every 6 h orally or intramuscularly for 24 h. All were markedly improved at 12 h (symptom score 1.0 +/- 0.3, p less than 0.001, range 0 to 3), but symptoms increased after the drug was discontinued at 24 h (symptom score = 2.4 +/- 0.5). We conclude that dexamethasone in a dosage of 4 mg PO or IM every 6 h is an effective treatment for AMS, but that illness may recur with abrupt discontinuation of the drug.