Abstract Some arsenic compounds were the first antimicrobial agents specifically synthesized for the treatment of infectious diseases such as syphilis and trypanosomiasis. More recently, arsenic trioxide has been shown to be efficient in the treatment of acute promyelocytic leukemia. The exact mechanism of action has not been elucidated yet, but it seems to be related to arsenic binding to vicinal thiol groups of regulatory proteins. Glutathione is the major intracellular thiol and plays important roles in the cellular defense and metabolism. This paper reports on a study of the interactions between arsenic(III) and either cysteine or glutathione in aqueous solution. The behavior observed for the As(III)–glutathione system is very similar to that of As(III)–cysteine. In both cases, the formation of two complexes in aqueous solution was evidenced by NMR and electronic spectroscopies and by potentiometry. The formation constants of the cysteine complexes [As(H −1Cys) 3], log K=29.84(6), and [As(H −2Cys)(OH) 2] −, log K=12.01(9), and of the glutathione complexes [As(H −2GS) 3] 3−, log K=32.0(6), and [As(H −3GS)(OH) 2] 2−, log K=10(3) were calculated from potentiometric and spectroscopic data. In both cases, the [As(HL) 3] species, in which the amine groups are protonated, predominate from acidic to neutral media, and the [As(L)(OH) 2] species appear in basic medium (the charges were omitted for the sake of simplicity). Spectroscopic data clearly show that the arsenite-binding site in both complexes is the sulfur atom of cysteine. In the [As(L)(OH) 2] species, the coordination sphere is completed by two hydroxyl groups. In both cases, arsenic probably adopts a trigonal pyramidal geometry. Above pH 10, the formation of [As(OH) 2O] − excludes the thiolates from arsenic coordination sites. At physiological pH, almost 80% of the ligand is present as [As(HL) 3].