A 72-h time-course study was conducted to elucidate the physiological mechanism underlying cysteine (Cys) toxicity in chicks beginning at 8-d posthatch. Biochemical markers quantified in plasma and liver samples collected from chicks receiving 30 g/kg excess dietary Cys were compared with baseline measurements from chicks receiving an unsupplemented corn-soybean meal diet over a 72-h feeding period. Concomitant with chick mortality were indices of acute metabolic acidosis, including a rapid increase (P < 0.001) in anion gap that resulted from a reduction (P < 0.001) in plasma HCO(3)(-) of approximately 40% and a 2.8-fold increase (P < 0.001) in plasma sulfate in chicks receiving excess Cys. Additionally, provision of 30 g/kg excess Cys resulted in a 1.5-fold increase (P < 0.05) in hepatic oxidized glutathione compared with the 0-h control time-point. Excess dietary Cys did not affect plasma free Met, but plasma free Cys increased (P < 0.05) from 89 to 107 mumol/L at 12 h and remained elevated through 36 h. Strikingly, ingestion of 30 g/kg excess Cys caused more than a doubling (P < 0.001) of plasma free cystine, the oxidized form of Cys, beginning 12 h after initiating the study, and it remained elevated throughout the 72-h feeding period. Taken together, these data suggest that ingestion of 30 g/kg excess l-Cys causes both acute metabolic acidosis and oxidative stress in young chicks when fed a nutritionally adequate, corn-soybean meal diet.