SYSNOPSIS[Methylene-14C]-L-tryptophan was administered intravenously to five patients suffering from severe depression before and after clinical recovery, and to six control subjects; all subjects were tested while on a standard diet. [14C]-5-Hydroxyindoleacetic acid and [14C]-indoleacetic acid were isolated from urine during the following 48 hours and purified to constant specific radioactivity (SA). From the SA and the determination of the total excretion of the two acids their percentage conversion from labelled tryptophan was estimated. There was no consistent difference found, in patients before and after recovery, or between patients and controls, in the conversion of tryptophan to these indole acids. In another series of 11 depressive patients and 11 controls, plasma total (acid-soluble) tryptophan was measured at frequent intervals up to three hours after intravenous administration of a loading dose (1 g) of L-tryptophan. The height of the curves of plasma tryptophan throughout the three hour period was greater than in the depressive patients, even after they had recovered, than in the controls. It is concluded that the apparent volume of distribution of tryptophan is reduced in depressive individuals. This is consistent with other findings of increased protein-binding of plasma tryptophan and reduced CSF tryptophan levels in depressive patients.