The bladder wall becomes to ischaemic when intravesical pressure rises above capillary pressure. This will occur routinely in bladders with outflow obstruction. Experiments in vitro show that the detrusor normally uses anaerobic as well as aerobic metabolism. Anoxic conditions result in an initial reduction in contractility, but significant contractile ability persists. Substrate removal causes a slow progressive fall in contractility as glycogen stores deplete. Removal of substrate and oxygen causes rapid loss of contractile ability and permanently damages intrinsic nerves, although the detrusor recovers well. In vivo ischaemia in animal models results in bladder overactivity and the expression of apoptotic markers in intrinsic neurons in the bladder wall. In humans, bladders from patients with bladder instability show patchy denervation, suggesting that periodic ischaemia and neuronal death may predispose to overactivity.