L-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, was administered at a dose of 0.15 and 0.45 mmol/kg to healthy volunteers. The plasma concentration of OTC reached a peak between 45 and 60 min after p.o. administration. The p.o. clearance of 0.15 mmol/kg of OTC was 0.57 +/- 0.20 liters/(hr.kg) S.D.. The peak increase in plasma OTC was followed by an increase in the plasma concentration of cysteine which rose by 18 to 75 microM over the average basal concentration of 17 microM. The plasma concentrations of free glutathione and total glutathione (i.e., glutathione in small molecular and protein mixed disulfides) did not change significantly during 8 hr after the ingestion of OTC. In contrast, there was a significant increase in the average concentration of cysteine from 0.37 to 0.99 nmol/mg of protein and of glutathione from 8.7 to 15.6 nmol/mg of protein in lymphocytes 2 to 3 hr after ingestion of OTC. The present data shows that OTC is a prodrug of cysteine after p.o. administration in humans and that OTC can raise the circulating concentration of cysteine and the intracellular concentration of cysteine and glutathione in lymphocytes.