Effects of tumor, operative stress and tumor removal, and postoperative TPN of varying amino acid compositions on brain levels of tryptophan or tyrosine as predicted by their brain influx rates were studied in normals and in malnourished cancer patients. Concentrations of the large neutral amino acids (LNAA) were determined in patients before and after tumor removal, and in postoperative patients before and after receiving either a standard TPN solution (STD-TPN), or a branched-chain amino acid solution (BCAA-TPN). The LNAA were altered in all groups versus normals. Brain influx rates showed the following: in preoperative patients, predicted brain tryptophan levels were below normal (P less than 0.001), whereas tyrosine levels were within or above normal; no significant differences between pre- and postoperative tryptophan or tyrosine levels; postoperative STD-TPN did not change predicted brain tryptophan concentration from preinfusion values, but BCAA-TPN decreased it (P less than 0.001), underscoring the common transport carrier; and preinfusion predicted brain tyrosine levels were decreased (P less than 0.001) by both types of TPN solutions. These results imply low substrate levels for brain serotonin and catecholamine synthesis, possibly affecting functions dependent on their control.