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A (2′-5′)oligoadenylate-dependent endoribonuclease (RNase L) is an important mediator of interferon's antiviral actions. Levels of this enzyme were determined in spleen, lung, liver, and kidney of mice at different times after birth. The levels of RNase L were found to be relatively low in newborn kidney, lung, and spleen. RNase L levels rise 2- to 10-fold in these three tissues as mice approach 5 days of age. In the spleen, levels of RNase L remain high as mice reach adult life. In the lung and kidney, however, RNase L levels decrease after 14 days. RNase L levels in the liver are highest from birth to 5–7 days and then decrease subsequently and remain low in adult mice. These changes in RNase L levels with postnatal development may be important with regard to age-specific susceptibility to some virus infections.