This study examined the dynamics for ammonia (NH3) metabolism in human skeletal muscle during and after intense one-legged exercise. Subjects (n = 8) performed dynamic leg extensor exercise to exhaustion (3.2 min). MuscleNH3 release increased rapidly to a maximum of 314 +/- 42 mumol/min and declined immediately on cessation of exercise. Recovery was complete in approximately 20 min. Arterial [NH3] increased less rapidly and reached itsmaximum 2-3 min into recovery. These data demonstrate that NH3 clearance is more sensitive to the cessation of exercise than is NH3 release from skeletal muscle. Muscle [NH3] increased three to fourfold during exercise and represented 74 +/- 8% of the total net NH3 formation. Thus the change in muscle [NH3] alone underestimates the NH3 production. There was no evidence that the muscle-to-venous blood NH3 ratio shifts in accordance with the H+ data. Thus other factors must contribute to the NH3 release from active muscle. The total net NH3 formed corresponded with the intramuscular inosine 5'-monophosphate accumulation, suggesting that the NH3 was derived from AMP deamination. Changes in the known modulators of AMP deaminase (ATP, ADP, H+) were moderate, so the mechanisms initiating the deamination remain obscure.