This study examined the effects of acclimatization to 4,300 m altitude on changes in plasma ammonia concentrations with 30 min of submaximal [75% maximal O2 uptake (V̇O2(max))] cycle exercise. Human test subjects were divided into a sedentary (n = 6) and active group (n = 5). Maximal uptake (V̇O2(max)) was determined at sea leavel and at high altitude (HA; 4,300 m) after acute (t<24 h) and chronic (t = 13 days) exposure. The V̇O2(max) of both groups decreased 32% with acute HA when compared with sea level. In the sedentary group V̇O2(max) decreased an additional 16% after 13 days of continuous residence at 4,300 m. whereas V̇O2(max) in the active group showed no further change. In both sedentary and active subjects, plasma ammonia concentrations were increased (P < 0.05) over resting levels immediately after submaximal exercise at sea level as well as during acute HA exposure. With chronic HA exposure, the active group showed no increase in plasma ammonia immediately after submaximal exercise, whereas the postexercise ammonia in the sedentary group was elevated but to a lesser extent than at sea level or with acute HA exposure. Thus postexercise plasma ammonia concentration was decreased with altitude acclimatization when compared with ammonia concentrations following exercise performed at the same relative intensity at sea level or acute HA. This decrease in ammonia accumulation may contribute to enhanced endurance performance and altered substrate utilization with exercise following acclimatization to altitude.