Leukocyte and plasma concentrations of free glutathione, cysteine, methionine, and taurine, and total glutathione and cysteine concentrations were determined in healthy human subjects before and during a seven-day period of total energy deprivation. In leukocytes a progressive decline in total glutathione concentration was found during seven days of starvation due to a decrease in free glutathione content. An increased mixed protein-bound glutathione concentration was calculated, whereas the total cysteine level was unaltered. Fasting resulted in a decreased plasma concentration of free glutathione, whereas the total glutathione level remained unchanged. Free leukocyte concentrations of taurine and methionine were reduced, whereas plasma sulfur amino acid levels were essentially unaffected. These results probably reflect a limited availability of sulfur amino acids during fasting, when glutathione is used as cysteine reservoir for synthesis of other vital sulfur containing compounds. The potential use of leukocyte glutathione, methionine, and taurine concentrations as intracellular indicators of sulfur amino acid deficiency are stressed.