The effect of hemorrhagic shock, hypoxemia and anoxia on the levels of adenine and pyridine nucleotides of liver and kidney was assessed. ATP levels in liver and kidney in shock or animals subjected to 7 min of anoxia decreased by 85 and 73%, respectively. Under hypoxic conditions (arterial P(O2) at 18 mmHg), the decrease was only 62 and 48% in liver and kidney, respectively. Tissue NAD levels decreased and NADH levels increased during shock but were found to be essentially unaltered during experimental hypoxemia. Thus, shock produced greater alterations in adenine and pyridine nucleotides than did hypoxemia alone, indicating that stagnant hypoxemia due to shock is more deleterious to energy metabolism than is severe hypoxemia with an otherwise normal circulation. The results also suggest that if an arterial P(O2) of 18 mmHg represents the initial stages of tissue hypoxia, then tissue ATP levels are a more sensitive indicator of this than NAD levels.