The plasma concentrations of branched-chain and aromatic amino acids have been measured in two different types of sustained dynamic exercise. Twenty-two subjects participated in the 1986 Stockholm Marathon and eight subjects took part in an army training programme of approximately 1.5-h duration. Both types of exercise caused a significant decrease in the plasma concentration of branched-chain amino acids, while there was no change in the concentration of total (free plus bound to albumin) tryptophan. The plasma concentration of free tryptophan, which was measured in the marathon runners, was found to increase 2.4-fold during the race. This increase is probably caused by a pronounced elevation in the concentration of plasma free fatty acids during exercise, since these are known to displace tryptophan from albumin. The observed increase in plasma free tryptophan concentration, together with the decrease in plasma concentration of branched-chain amino acids, gives rise to a marked increase in the plasma concentration ratio of free tryptophan/branched-chain amino acids. This should lead to an increase in the rate of transport of tryptophan across the blood-brain barrier and hence to an increase in the rate of synthesis of 5-hydroxytryptamine (5-HT) in the brain. An elevated concentration of 5-HT in specific areas of the brain may be responsible, at least in part, for the development of physical, and/or mental fatigue during prolonged exercise.