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1. The effects of the loss of normal activity can be studied in muscles held in a shortened position by immobilizing the ankle in a plaster cast. Since the innervation remains intact with this procedure, removal of the restraining case allows normal activity to be restored. The soleus and plantaris muscles grew as a function of time after the return of normal activity and these changes in tissue size are explained by changes in the average rates of protein synthesis and protein break-down as measured by sensitive in vitro techniques. Activity stimulates protein synthesis and inhibits protein break-down of the soleus muscle, thus enabling the tissue to accumulate protein. Blockage of de novo synthesis of RNA, but not DNA, severely restricted the normal, rapid enhancement of protein synthesis after thr return of activity. 2. The return of isotonic activity to the extensor digitorum longus muscle after immobilization in a lengthened position failed to fully compensate for the loss of the growth-promoting influence of stretch and the tissue gradually returned to the size of the control muscle. During the recovery process the higher rate of protein turnover and RNA concentrations of the immobilized muscle returned to the lower values of the control.

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