Tumbling pentobarbital-anesthetized rats (25 mg/kg) in a Noble-Collip drum for 600 revolutions resulted in a severe form of circulatory shock, and all traumatized rats died within 5 hours. However, rats subjected to sublethal tumbling (i.e., conditioning) for 4 days before lethal tumbling developed tolerance to this usually lethal dose of trauma. After the tumbling, untreated nonconditioned rats showed a marked production of the cardiotoxic peptide, myocardial depressant factor (MDF), and depression of reticuloendothelial system (RES) function. Conditioned rats subjected to trauma did not show these changes. Nonconditioned tumbled rats developed severe twisting of the small intestine resulting in a vascular strangulation of the intestine: conditioned rats did not exhibit strangulation after tumbling. To eliminate mesenteric strangulation during tumbling, two methods were employed: 1) a four-baffle drum to prevent torsional twisting of rats in the drum; and 2) emptying the intestinal contents before tumbling in the ordinary two-baffle drum. Both of these procedures eliminated mesenteric strangulation in rats during tumbling, and all rats subjected to either of these procedures survived 5 hours post-trauma. Thus mesenteric strangulation may be a critical factor contributing to lethality in Noble-Collip drum trauma. Post-traumatic splanchnic lysosomal labilization, depression of RES function, and pancreatic MDF formation and its accumulation in the plasma may be direct consequences of the splanchnic ischemia leading to lethal shock. Since conditioned rats did not develop mesenteric ischemia during tumbling, no subsequent detrimental event occurred, and these rats did not develop lethal circulatory shock.