The x-irradiation of a dilute suspension of erythrocytes results in a decrease in the glyoxalase activity of the cells as a result of a fall in the reduced glutathione level. The present paper deals with the possible role of H~O2 in this reaction.The addition of intact erythrocytes to physiological saline previously irradiated with 150,000 r or 225,000 r results in a fall in the glyoxalase activity of the ceils. The inhibition is prevented by thepreincubation of the irradiated saline with catahse and is reversed by the addition of plasma, glucose, adenosine, and inosine to the cell suspension.An inhibition of the glyoxalase activity is also produced by the addition of Hg)2 to the suspension of erythrocytes. The inhibitory effect of H202 can be prevented and largely reversed by plasma, glucose, adenosine, and inosine. Methylglyoxal is also protective under these conditions.Hydrogen peroxide formed continuously and in low concentrations by enzyme systems appears to be more effective than added H~3~ in inhibiting the glyoxalase system. The inhibition by H~)v-producing enzyme systems is minimized by the addition of catalase, plasma, glucose, methylglyoxal, and to a lesser extent, by adenosine and inosine, and is accentuated by the addition of sodium azide.The results are discussed in relation to the role of H~O~ and catalase in the toxicity of ionizing radiations.The formation of hydrogen peroxide by the irradiation of aqueous solutions has been observed repeatedly (1, 2) and the considerable influence of this substance on many biological systems has encouraged a great deal of speculation, and considerable experimentation towards elucidating the role, if any, of H~O9 in the toxicity of ionizing radiations. The glyoxalase activity of intact erythrocytes is inhibited by x-radiation largely as a result of a decrease in the reduced glutathione level of the cells (3).