The Krogh capillary-tissue cylinder arrangement has been modeled and solved to include interaction between the capillary and tissue. Sophisticated, distributed, and simple lumped parameter equations have been used to describe the system. Solutions have been investigated using digital, analog, and hybrid computer techniques. Results from the simulations have been compared with experimental tissue response data obtained with oxygen microelectrodes inserted in the brain of anesthetized, curarized cats. Comparisons indicated that autoregulatory mechanisms play an important role in determining the characteristic tissue oxygen tension response to arteriole oxygen tension upsets. Theoretical control mechanisms have been postulated and superimposed on the capillary-tissue models to explain the temporal behavior of brain oxygen tension during conditions of anoxic-anoxia. Preliminary evidence indicates an active, inhibitory (Protective) mechanism for oxygen in brain. A hybrid computer simulation of interacting regions of brain gives a possible explanation for such a mechanism.