Exercise requires the integrated activity of neuromuscular systems controlling skeletal, cardiac, and vascular smooth muscle. However, exercise can be defined at the most basic cellular level. Therefore, in order to effectively study the specific cellular events involved in the activity of each system, it is necessary to first isolate and control the major neurogenic, myogenic, and humoral components of neuromuscular activity. For example, these components of activity are differentially involved in the regulation of skeletal muscle acetylcholine receptors. The increased concentration of intracellular free calcium during contraction (an event classified as a myogenic component of activity), rather than trophic factors from the motoneuron (neurogenic component) and hormonal factors (humoral component), is a major regulator of acetylcholine receptor expression. The degree of experimental control increases as one progresses from the experimental approaches involving the exercising human to the single cell studied in vitro. It has been possible only by cell culture techniques to identify specific intracellular messengers, e.g., calcium, that mediate the effect of neuromuscular activity on acetylcholine receptor expression. The wide variety of in vitro techniques now available permit the selection of appropriate models. Therefore, the use of various in vitro methods by exercise physiologists seems justified. In vitro methods provide a valuable dimension to the study and understanding of neuromuscular activity in the intact organism.