The structure of lumbricals of the rat has been investigated with respect to cholinesterase (ChE) and the known hypersensitivity of sarcolemma to acetylcholine (Ach) upon denervation of the muscle. ChE associated with the junctional sarcolemma undergoes a marked decrease in its activity in denervated muscles as detected by a histochemical reaction at electron microscopical level. This activity is inhibited by BW 284 C51, a specific inhibitor of acetylcholinesterase (AchE). It appears therefore that the histochemical reaction used in this study detects specific ChE, i.e. AchE. The relevance of the decrease in ChE upon denervation to the known molecular forms of ChE is discussed. The structure of the sarcolemma in the region of the neuromuscular junction shows no apparent change in the number of intramembranous particles upon denervation that could be visualized in replicas of the freeze-fractured material examined by transmission electron microscopy, thereby indicating that the intramembranous particles are not directly related to the ChE molecules. The extra-junctional sarcolemma of the denervated muscle shows 15-18 nm (ca. 15 nm) intramembranous particles on the plasmic half of the fractured faces (P face) discernible in electron micrographs of replicas. These particles are often clustered, and the number of particles in these clusters varies from 4 to 50. In contrast, the corresponding fractured face of the contralateral controls shows mostly ca. 8 nm particles dispersed throughout the fractured face of the extra-junctional sarcolemma, there being few ca. 15 nm particles. On the basis of the known muscle physiology and biochemistry, it is most likely that ca. 15 nm particles represent an incorporation of newly synthesized Ach receptors in the extra-junctional sarcolemma after denervation of the muscle. These particles appear to be preferentially attached to the P face of the sarcolemma, there being no depressions on the exoplasmic fractured half (E face) in metallic replicas.