The effects of whole body x-irradiation and corticosteroid administration on the ribonuclease system of mouse and rat thymus and liver are reported. The total levels of alkaline and acid ribonuclease, the level of the alkaline ribonuclease inhibitor and the level of alkaline ribonuclease in a free or active state have all been measured. The approach used emphasised the importance of enzyme and inhibitor balance in determining the actual amount of alkaline ribonuclease free to act in the tissue homogenates. In the first hours after irradiation of mice with 400-900 rad, there was no change in the total levels of alkaline ribonuclease or acid ribonuclease in the thymus. However, the inhibitor was partially inactivated, leading to an increase in the amount of alkaline ribonuclease in an active state. In the more radioresistant liver, the changes were much smaller. Inhibitor inactivation preceded cell destruction, was dose dependent and preventable by a radioprotective drug. Cortisone injection did not produce a comparable effect. A similar change could be produced in rat thymus, but only with relatively high radiation doses. The conclusion was that ribonuclease activation, mediated by destruction of the labile inhibitor, could be a step in radiation injury to mouse thymic lymphocytes but was unlikely to be important in the rat. The activation of a broad spectrum of lytic enzymes by inhibitor destruction should be further investigated as a mechanism of radiation injury.

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