Infections and acute mountain sickness (AMS) are common at high altitude, yet their precise etiologies remain elusive and the potential for differential diagnosis is considerable. The present study was therefore designed to compare clinical nonspecific symptoms associated with these pathologies and basic changes in free radical and amino-acid metabolism. Nineteen males were examined at rest and after maximal exercise at sea level before (SL(1)/SL(2)) and following a 20 +/- 5 day ascent to Kanchenjunga base camp located at 5100 m (HA). Four subjects with symptoms consistent with an ongoing respiratory and recent gastrointestinal infection were also diagnosed with clinical AMS on the evening of day 1 at HA. These and six other subjects recovering from symptoms consistent with a respiratory infection presented with a greater increase (HA minus SL(1)) in AMS scores and resting venous concentration of lipid hydroperoxides (LH) and in total creatine phosphokinase and ratio of free tryptophan/branched chain amino acids, and greater decrease in glutamine (Gln) compared to healthy controls (n = 9, p < 0.05). The decrease in Gln was consistently related to the altitude/exercise-induced increase in LH (r = -0.69/r = -0.45; p < 0.05) and altitude-induced increase in myoglobin (r = -0.73, p < 0.05). These findings highlight the potential for the misdiagnosis of altitude illness due to the similarity of nonspecific constitutional symptoms associated with infection and AMS. Both conditions were characterized by parallel changes in peripheral biomarkers related to free-radical, skeletal muscle damage and amino acid metabolism. While clearly not establishing cause and effect, free radical-mediated changes in peripheral amino acid metabolism known to influence immune and cerebral serotoninergic function may enhance susceptibility to and/or delay recovery from altitude illness.