Oral administration of the serotonin precursor L-5-hydroxytryptophan with a peripheral decarboxylase inhibitor produced Mild to moderate improvement in six of seven chronic undifferentiated schizophrenic patients who were resistant to phenothiazine treatment, as compared to an oral administration of a placebo. Two of four chronic paranoid schizophrenic patients who were resistant to phenothiazine treatment became worse with 5-hydroxytryptophan, one improved. It is presumed that these psychological changes were directly or indirectly produced from increases in brain serotonin. Indirect data from animals and humans indicate that there may be an abnormality in serotonin metabolism in some schizophrenics. While our data are consistent with this hypothesis, other explanations for our data must be entertained.