More than 30 years ago, it was proposed that adenosine was released from skeletal muscle in response to a decrease in the oxygen supply-to-demand ratio. It has subsequently been confirmed that adenosine is released from red muscles in proportion to the contraction frequency, but the mechanism that controls its release remains controversial. There is no direct evidence for the involvement of oxygen insufficiency in the process, and there is some indirect evidence that it is not involved. On the other hand, there is direct evidence that a decrease in pH, with no change in oxygen supply-to-demand ratio, can stimulate adenosine release, and the amounts of adenosine released are well correlated with the pH change in all situations tested. A direct analysis of the role of hypoxia in adenosine release is therefore urgently needed.