Sulfur-containing compounds are used as rescue agents to protect normal tissue from the toxic side effects of cis-[PtCl₂(NH₃)₂] (cisplatin) without affecting its anti-tumour activity. Reactions of the model complexes [Pt(dien)Cl]⁺ (1) and [Pt(dien)(GSMe)]²⁺ (2) (GSMe = S-methylglutathione) with the rescue agents glutathione (GSH), thiourea, thiosulfate, and diethyldithiocarbamate (DDTC) have been studied in a 1.0 mol dm⁻³ aqueous perchlorate medium at 37 °C and pH 7.30 using stopped-flow and conventional UV/VIS spectrophotometry. The reactions of 1 with 2-mercaptoethanesulfonate (mesna) and 2-mercaptoethylamine (cysteamine), which is the parent compound of 2-(3-aminopropylamino)ethylphosphorothioic acid (WR2721), and of cis-[Pt(NH₃)₂(GSMe)₂]²⁺ with thiosulfate have also been studied. The reactions between cisplatin and DDTC, thiourea and thiosulfate were investigated in an unbuffered 0.10–0.05 mol dm⁻³ chloride medium at 37 °C. All reactions follow the rate law: −d[complex]/dt = k₂[Pt(II)][Nu] where k₂ denotes a second-order rate constant and [Nu] is the total concentration of nucleophile. The rate law indicates that the reactions proceed via a direct nucleophilic substitution pathway. The rescue agents display a relatively narrow range of reactivity towards 1, mesna < Hcysteamine < GSH < thiourea < thiosulfate < DDTC with rate constants k₂ of 0.156 ± 0.001, 0.22 ± 0.01, 0.237 ± 0.003, 1.17 ± 0.01, 5.57 ± 0.04, and 8.0 ± 0.1 mol⁻¹ dm³ s⁻¹, respectively. The sequence is consistent with the report that DDTC is the most effective rescue agent discovered so far when administered after cisplatin. The activation parameters ΔH^≠ and ΔS^≠ have been determined and the products of the reaction of 1 with the rescue agents have been characterised.