Acute compartment syndrome (ACS) is a devastating complication of rhabdomyolysis caused by muscle tamponade secondary to increased intracompartmental pressure (Pi). ACS requires emergency surgical decompression when Pi greater than 30 mmHg (normal less than 4.0 mmHg) and clinical signs exist. The present study was undertaken to examine whether mannitol which has been used extensively for prevention of acute renal failure in rhabdomyiolysis may also improve muscular hemodynamics in ACS. ACS was produced in dogs by injecting dog plasma into the anterolateral compartment of the hind limb. The Pi was directly monitored. Control dogs received saline, whereas experimental dogs received intravenously 20% mannitol (0.15 ml/min/kg) over a period of 1 h. The initial Pi was set arbitrarily at 100 mm Hg. Following the establishment of ACS, the spontaneous mean decrease in Pi in the control group was 40% of initial value over 60 min (n = 5) versus a decrease of 65%/60 min in the experimental (mannitol) group (n = 7, p less than 0.01). The net mean decompressive effect of mannitol treatments was approximately 28 mm Hg (mean control Pi minus mean experimental Pi at time 60 min). Extrapolated to man with ACS, such a decrease in Pi induced by mannitol theoretically could relieve compartmental tamponade noninvasively.