Using a monoclonal antibody (6.17) directed against a Schwann antigen, we have shown that Schwann cells synthesize a molecule implicated in a change of expression of synaptic cholinesterases, AChE and BChE, during muscle differentiation. In vitro, during synaptogenesis, the two enzymes are first present at developing synapses, and addition of Schwann cells to muscle-neuron co-cultures induces a disappearance of BChE, leaving only AChE activity as in the adult neuromuscular junction. This effect is inhibited by the 6.17 antibody. Thus, a molecule produced by Schwann cells is involved in the maturation of the neuromuscular synapse, in addition to the neuronal factors (CGRP, ARIA/heregulin, agrin), which are known to control the synthesis, maturation and accumulation of acetylcholine receptors and other synaptic components. In addition, in vivo, in the newborn rat, butyrylcholinesterase and acetylcholinesterase activities are initially present in equal amounts in the neural zone, but butyrylcholinesterase levels diminish sharply between 7 and 15 days after birth, the stage at which the synaptic Schwann cell membrane becomes juxtaposed with the muscle membrane.