Calcitonin gene-related peptide (CGRP) acts as an anterograde trophic agent which regulates skeletal muscle acetylcholine receptor function. We examined whether CGRP also influences other synaptic transmission-related molecules, i.e. acetylcholinesterase (AChE) forms. Results show that: (a) CGRP associated with rat anterior gracilis muscle endplates declines following obturator nerve transection; (b) exogenous CGRP treatment has a selective, innervation-like effect on the globular tetramer (G4) of AChE in gracilis motor endplates; and (c) this effect is reversed by the CGRP receptor antagonist hCGRP8-37. We conclude that exogenous CGRP, and/or a biologically active CGRP fragment(s), influences G4 AChE levels through specific CGRP-CGRP receptor interactions. This conclusion is consistent with the notion that motor nerve-derived CGRP participates in the trophic control of G4 AChE at the neuromuscular junction.