It has been proposed by Saltin (38) that oxygen delivery by blood is limiting for maximal work and oxygen consumption in humans during whole body exercise (e.g., cycling), but not during single muscle (quadriceps) exercise. In order to test this prediction quantitatively, in the present article a static (steady-state) computer model of oxygen transport to and within human skeletal muscle during single muscle (quadriceps) exercise and whole body exercise (cycling) is developed. The main system fluxes, namely cardiac output and oxygen consumption by muscle, are described as a function of the 'primary' parameter: work rate. The model is broadly validated by comparison of computer simulations with various experimental data. In silico studies show that, when all other parameters and system properties are kept constant, an increase in the working muscle mass from 2.5 kg (single quadriceps) to 15 kg (two legs) causes that at some critical work intensity oxygen concentration in muscle cells drops (very near) to zero and therefore oxygen supply by blood limits maximal oxygen consumption and oxidative ATP production. This causes that the maximal oxygen consumption per muscle mass is significantly higher during single muscle exercise than during whole body exercise. The effect is brought about by a distribution of a limited amount of oxygen transported by blood in a greater working muscle mass during whole body exercise.