1 After D and L-tryptophan (50 mg/kg) were given intravenously in the dog, the concentration of the amino acid was increased in ventricular cerebrospinal fluid (CSF) during the subsequent 4 h or sampling, although the concentrations were significantly lower following the administration of the D-isomer. 2 There was no evidence that D-tryptophan increased the synthesis of 5-hydroxytryptamine (5-HT) in dog brain as judged by the failure to cause a change in 5-hydroxyindoleacetic acid (5-HIAA) concentrations in ventricular CSF different from that seen with controls. 3 There was no appreciable conversion of D-tryptophan to L-tryptophan in the dog. 4 D-tryptophan was cleared more rapidly from plasma than L-tryptophan. 5 No difference in plasma binding between D and L-tryptophan was detected.