A method for the measurement of free and bound cyst(e)ine and the sum thereof has been developed. In adult human blood, cyst(e)ine is distributed equally between that which is bound to plasma proteins and that which is free. Cyst(e)ine is bound predominantly to albumin, and this binding is not an in vitro artifact. Cysteine bound to plasma proteins may be displaced by homocysteine which competes for the available sulfhydryl groups of plasma proteins. Rats starved for 8 days had a significant decrease in both plasma free cyst(e)ine and bound cysteine. These data suggest that present methods for the determination of plasma cyst(e)ine under-estimate the quantity of cyst(e)ine in the plasma available for cellular metabolism.