Rats and guinea pigs were injected with 2,4-dichlorophenoxyacetate (2,4-D) in amounts sufficient to keep them myotonic for over 12 hr daily. The biceps brachii muscles were studied by histochemistry, epoxy resin histology, and electron microscopy after one to five days. Changes observed include proliferation of the longitudinal component of the sarcoplasmic reticulum, production of new myofilaments on the periphery of cells and in nuclei, activation of satellite cells, accumulation of lipid droplets, myofibrillar damage with Z-disc streaming, necrosis, and regeneration. The action mehanisms of 2,4-D are not well understood. Some of the phenomena observed could be classified as proliferative and may be analogous to the auxin action of 2,4-D in plants. The production of intranuclear filaments is probably related to the diffusion of newly formed cytoplasmic proteins into nuclei.