One hundred years ago, in 1897, Sherrington adopted the name synapse. However, the concept of the synapse emerged from considerations of how muscles are contracted and so locomotion affected over a period of 2400 years, from the time of Plate and Aristotle in the 4th century BC to the early part of the 20th century. This early history is considered in the present review. In terms of duration of influence, the early history was dominated by Aristotle's concept of vital pneuma, This was derived from the ether which filled all space, taken in by the lungs, transformed to vital pneuma in the heart, and then conducted in the blood stream to be transmitted to muscles. The vital pneuma then initiated the final phase of the muscle's psyche, that is, its contraction leading to locomotion. Aristotle's ideas had to be modified with the discovery by Galen and his students in the 2nd and 3rd centuries AD that nerves arising from the brain and spinal cord are necessary for the initiation of muscle contraction. They modified the Aristotlean account so that the vital pneuma delivered by blood vessels to the brain was converted there to psychic pneuma, from whence it was conducted along nerves to be transmitted to muscle, so allowing the muscle to contract. There matters rested for about 1300 years until Descartes. Descartes rejected the idea of organs and muscles possessing a psyche with a final cause that was released by the conduction and transmission of psychic pneuma in nerves, emphasising that mechanical explanations must be sought when determining the function of an organ or muscle. He argued in his corpuscular theory that fine particles derived from the blood in the brain, which he gave the unfortunate name of animal spirits, were conducted and transmitted along nerves to enter muscle during transmission, so leading to the increase in width of the muscle fibres, their shortening and contraction. This description was elaborated on in great detail by Descartes, and by his contemporary Borelli, in the 17th century.:ln the 18th century, Swammerdam carried out a series of brilliant experiments that showed that the Descartes/Borelli theory could not be correct, muscles did not change their volume during contraction, and so could not be contracted by being swollen due to an influx of the corpuscles that made up the animal spirits. These results were published at about the time of the birth of Galvani (1737), whose work was to show that animal spirits were not corpuscular but electrical. The triumph of 19th century physiology, primarily due to Matteucci, du Bois-Reymond and Helmholtz,was to take Galvani's discoveries and show that nerves possessed a potential across their walls that could give rise to a propagating transient potential change which was transmitted to muscles With a finite velocity. Although Sherrington refined the concept and adopted the word "synapse": at the end of that century, it was not until the early part of the 20th century that a conceptual scheme for the synapse involving transmitters and receptors was developed. This:clearly delineated a new period following the early history of synaptic transmission. (C) 1999 Elsevier Science Inc.