It has been shown that adenosine stimulates glycolysis in some cells and this ability of adenosine was tested in the hypoxic guinea pig heart. 2. Adenosine (10 microM) activated lactate production in the isolated perfused guinea pig heart under conditions of normoxia but did not under hypoxia. 3. Despite this, the nucleoside favorably influenced the energy metabolism of the hypoxic heart as revealed by the better posthypoxic functional recovery (98%) compared to the control without adenosine (78%). 4. Our findings suggest a role for the glycolytic pathway in this effect of the nucleoside as long as other cardiac energy-yielding pathways are strictly aerobic.