Summary: Blood plasma of man, rabbit, mouse, rat and guinea‐pig contains 3 groups of thiol compounds. Non‐protein thiols are present to the extent of approximately 52%. The albumin fraction contains 75% thiols as determined with di‐(5‐carboxy‐4‐nitrophenyl) disulphide and about 10% higher values are obtained when determinel with 4,4′‐dipyridyldisulphide. Approximately 20% of the plasma thiols are present in proteins other than albumin.The reaction of the plasma thiols with the disulphides is mainly due to mercaptalbumin, and the reactivity of plasma thiols and the isolated albumins with di‐(5‐carboxy‐4‐nitrophenyl) disulphide and 4,4′‐dipyridyldisulphide varies according to species and pH. Human and guinea‐pig mercaptalbumin react slowly with di‐(5‐carboxy‐4‐nitrophenyl) disulphide at pH 6·5 whereas a fast reaction takes place with rat's mercaptalbumin. Intermediate reaction rates are seen with rabbit and mouse plasma.Species differences are also noted in the unmasking of thiol groups of plasma and isolated albumins by urea, guanidine hydrochloride and lauryl sulphate.Certain positions of the thiol groups in the mercaptalbumin structures are suggested and genetic considerations and evolutionary aspects of mercaptalbumin coding are discussed.