Possible causal factors of denervation-induced changes in muscle include inactivity, products of nerve degeneration and lack of a nerve-borne trophic agent. We now show that if the innervated fibres in a partially denervated rat muscle are rendered inactive, they undergo a reaction as intense as that of the denervated fibres. This provides further support for the view that the effects of denervation on the extrajunctional muscle membrane result from a combination of muscle inactivity and of nerve breakdown products acting diffusely throughout the muscle.