In an attempt to define alterations in cellular metabolism associated with growth hormone deficiency, we have studied the alkaline RNAase activity in the liver subcellular fractions from normal and hypophysectomized (hypox) adult and weanling rats. The total RNAase activity of the liver and kidney subcellular fractions was determined in adult and weanling rats maintained in a fed or fasted (15-hr) state. In the adult rat, RNAase activity/g tissue increased following hypox in each of the liver subcellular fractions with the soluble fraction exhibiting an approximate two-fold increase. Part of the increased activity was real due to an increase in the specific activity of the enzyme and part was apparent due to decreased liver weight following hypophysectomy. RNAase activity of the microsomal fraction of the adult rat kidney increased following both hypox and fasting; however, the largest increase appeared secondary to hypophysectomy. In the weanling rat, RNAase activity was increased only in the nuclear and soluble fraction of the fasted hypox rat liver. The nuclear and soluble fraction exhibited a two-fold increase in activity over comparable fractions from normal and normal fasted rat liver. The increased activity was real due to increased specific activity of the enzyme and apparent due to decreased liver weight. RNAase activity of the soluble fraction of weanling rat kidney increased in the normal fasted, hypox, and hypox fasted rat. This increase in the kidney was only apparent secondary to decreased renal weight following fasting and/or hypox. Liver RNAase activity returned to normal levels in the nuclear and soluble fraction from fasted weanling hypox rat liver following treatment with hGH but not with thyroxine or estradiol. It is concluded: (a) hGH deficiency results in real and apparent alterations of liver RNAase activity, (b) alterations in RNAase activity may be important in the mechanism of action of hGH but factors such as age and fasting are important modifiers of the system.