It is well known that prolonged passive muscle stretch reduces maximal muscle force production. There is a growing body of evidence suggesting that adaptations occurring within the nervous system play a major role in this stretch-induced force reduction. This article reviews the existing literature, and some new evidence, regarding acute neurophysiological changes in response to passive muscle stretching. We discuss the possible contribution of supra-spinal and spinal structures to the force reduction after passive muscle stretch. In summary, based on the recent evidence reviewed we propose a new hypothesis that a disfacilitation occurring at the motoneuronal level after passive muscle stretch is a major factor affecting the neural efferent drive to the muscle and, subsequently, its ability to produce maximal force.