This study used an experimental model (canine hind limb) of compartment syndrome, monitored with phosphorus 31 nuclear magnetic resonance spectroscopy, to determine the pressure threshold for metabolic deterioration in skeletal muscle previously subjected to ischemia. Our results show that muscle subjected to 6 h of antecedent ischemia has a lower tolerance to increased tissue pressure than otherwise normal muscle. The threshold was found to occur at a delta P (difference between mean blood pressure and limb compartment pressure) of 40 mm Hg, compared with a delta P of 30 mm Hg in muscle that was not subjected to antecedent ischemia. In addition, once the critical pressure threshold of postischemic muscle was crossed, there was a more rapid rate of high-energy phosphate depletion than that seen in normal muscle pressurized to the same degree beyond its delta P threshold. For compartment syndromes that appear after relatively atraumatic ischemia (i.e., drug overdose-induced limb compression, proximal arterial trauma causing distal limb ischemia, etc.), of < or = 6 h, fasciotomy should be performed at a delta P < or = 40 mm Hg. Compartment pressure elevation after local blunt muscle trauma and ischemia may well require earlier or even prophylactic fasciotomy. Fasciotomy in ongoing postischemic compartment syndromes should be considered particularly urgent owing to the rapid rate of metabolic deterioration that is observed once the critical delta P threshold is crossed. The type of compartment syndrome should always be considered when interpreting tissue pressure measurements as indications for fasciotomy.