The data presented here suggest that control of human brain 5HT synthesis by precursor availability is similar to that in the rat. Plasma tryptophan controls the brain level, although the plasma-brain relationship is modified by other large neutral amino acids in plasma. In normal circumstances brain tryptophan is an important factor controlling the synthesis of 5HT and tryptamine in human brain. However, the elevated brain tryptophan in patients with chronic liver disease does not lead to an increase in the rate of 5HT metabolism. In human brain the rate of tryptamine synthesis is normally aobut 10-20% of the rate of 5HT synthesis. Tryptamine metabolism is more sensitive than 5HT metabolism to changes in brain tryptophan. This is especially apparent after a tryptophan load. Our results suggest that tryptophan administration increases indoleamine function, as well as indoleamine synthesis, in depressed patients. Whether physiological variations in brain tryptophan in normal people are responsible for variations in indoleamine function is an open question.