Technical Abstract: BACKGROUND: Children with severe edematous malnutrition have higher than normal oxidant damage and lower concentrations of the antioxidant reduced glutathione (GSH), which are associated with slower synthesis of GSH and with low extra- and intracellular concentrations of the precursor amino acid cysteine. OBJECTIVE: We tested whether early dietary supplementation with cysteine could restore a normal GSH concentration and synthesis rate in these children. DESIGN: Erythrocyte cysteine and GSH concentrations and the fractional and absolute synthesis rates of GSH were measured in 2 groups of 16 edematous malnourished children, 10 boys and 6 girls aged 6-18 mo, at 3 times after hospital admission: at approximately 2 d (period 1), when they were malnourished and infected; at approximately 11 d (period 2), when they were malnourished but cleared of infection; and at approximately 50 d (period 3), when they had recovered. Supplementation with either 0.5 mmol. kg(-1). d(-1) N-acetylcysteine (NAC group) or alanine (control group) started immediately after period 1 and continued until recovery. RESULTS: From period 1 to period 2 the concentration and the absolute synthesis rate of GSH increased significantly (P < 0.05) in the NAC group but not in the control group. The increases in the GSH concentration and synthesis rate were approximately 150% and 510% greater, respectively, in the NAC group than in the control group. The increases in the NAC group were associated with a significant effect of supplement (P < 0.03) on erythrocyte cysteine concentration. CONCLUSION: These results suggest that the GSH synthesis rate and concentration can be restored during the early phase of treatment if patients are supplemented with cysteine.