Changes in hepatic and muscle high-energy phosphates in varying degrees of resting hypermetabolism were studied. Fourteen severely injured and five critically ill patients with normal blood pressure were investigated: the results were compared with 14 normal controls. ATP and ADP levels in the muscle were significantly changed in acutely severe injury: lactate and pyruvate levels in the liver and muscle increased; glycogen level in the liver decreased. Meanwhile, high-energy phosphates in both liver and muscle were not significantly changed in ongoing severe injury. Lactate level increased and glycogen level decreased in both tissues. In critical illness, hepatic and muscle ATP and ADP decreased significantly. The energy charge potential dropped. AMP, lactate, and the lactate-to-pyruvate ratio increased. Hepatic, but not muscle, glycogen dropped markedly. The correlation coefficient between hepatic and muscle ATP was 0.61; between hepatic ATP and hepatic glycogen was 0.60. Alteration in the ATP-ADP-AMP system in the liver and muscle suggests a low-energy charge in acute, severe injury and critical illness. This indicates a decreased capacity for biosynthetic reactions and production of storage compounds. The changes in high-energy phosphate in the liver always paralleled similar changes in muscle.