When a lowlander ascends to altitude and acclimatizes over days to weeks, both maximal exercise capacity and maximal cardiac output are reduced compared to sea level. Of the several possible mechanisms underlying this reduction of maximal cardiac output, the available data are interpreted as supporting the simplest hypothesis--that this merely reflects the reduced requirement for muscle blood flow that results from the arterial hypoxemia of altitude (which reduces muscle O2 availability and thus maximal muscle function). The competing hypotheses, that increased blood viscosity, reduced blood volume, autonomic nervous system changes or myocardial hypoxic dysfunction reduce maximal cardiac output, are not well supported by existing data. However, critical tests of some of these hypotheses remain to be devised and undertaken. When it comes to the question of the importance of reduced maximal cardiac output to V(O2) MAX at altitude, the available evidence suggests that cardiac output is not a major limiting variable. This is because as cardiac output rises, gains in convective flow of O2 in the circulation are offset by losses from greater diffusion impairment of O2 transfer in the lungs and muscles, and vice versa. However, just as with the mechanism of cardiac output reduction itself, clear-cut experimental tests of its role in limiting exercise at altitude remain to be conducted.