Studies were made on the oxidation of oxyhemoglobin (HbO2) by the presence of phenothiazine system tranquilizers.Methemoglobin (MHb) was formed when ethopropazine-HCl (I) [1094-08-2], promethazine-HCl (II) [58-33-3], promazine-HCl (III) [53-60-1], or perazine (VI) [84-97-9] was incubated with a suspension of human erythrocytes or with HbO2 solution obtained through hemolysis of this suspension.In either of the experiments with erythrocytes and HbO2 solution, the MHb-forming effect of the compound decreased in the order of I, II, III, and VI.The HbO2-oxidizing activity of these derivatives was enhanced when they were photoirradiated before mixing of the derivatives with HbO2 solutionChlorpromazine-HCl [69-09-0], methoxypromazine maleate [3403-42-7], thioperazine dimethanesulfonate [2347-80-0], fluphenazine dimaleate [3093-66-1], trimeprazine tartrate [2015-31-8], and methotrimeprazine-HCl [1236-99-3] formed MHb when their acid solutions were photoirradiated before their incubation with HbO2 solution.The HbO2-oxidizing activity of phenothiazine derivatives was also enhanced when they were subjected to potentiostatic electrolysis or pyrolysis.The amount of MHb formed in the incubation mixture paralleled the amount of semiquinone free radicals produced from the derivativesOn the basis of the results of comparative examinations on the HbO2-oxidizing activity, spectral change in the UV and visible regions, and polarog. half-wave potentials of the derivatives, it was presumed that, in the case where untreated phenothiazine derivatives were involved, cation radicals produced by some oxidizing substance in the incubation mixture played an important role in the formation of MHb from HbO2.