The integration between ion acid-base and metabolic regulation in skeletal muscle contracting high intensity is reviewed. The processes involved in the regulation of ion, acid-base and metabolic status within skeletal muscle cells during muscle contraction are intimately related. With the onset of muscle contraction many of these regulatory processes are simultaneously affected providing, initially, high force of contraction and a high rate energy supply. Continued contraction, and associated development of muscle fatigue, shows evidence of simultaneous changes in ion, acid-base and metabolic regulation which are involved in the downregulation of cellular function.