In summary, our immediate autopsy program provides a new tool for investigating the pathophysiologic effects of shock and trauma at the cellular and subcellular levels. By minimizing the time delay between death and tissue sampling with this technique, we have demonstrated the feasibility of validly applying the refinements of electron microscopy, histochemistry and analytical biochemistry to human tissue. Qualitative, semi-quantitative and quantitative data with these techniques have been integrated with clinical, physiologic and chemical studies on these patients during life. Cell injury produces an altered steady state of metabolism within the cell, evidence of which is seen in altered ultrastructure. If the injury is too severe, the cell will pass the "point-of-no-return," at which time the changes in the cell are no longer compatible with life and the cell dies and undergoes necrosis. Although the initiating injury and the patterns of the altered steady state may vary, once the cell has passed the "point-of-no-return," the patterns of cell injury regardless of the initial insult, are similar. We believe that the cellular patterns seen in patients dying from shock and trauma are remarkably similar to those produced by hypoxic tissue injury in experimental systems. Tissue from control patients in whom ischemic injury due to episodes of hypotension did not occur show good morphologic preservation with normal mitochondria and other cell organelles. Tissue from patients who have experienced acute shock consisting of a period of hypotensive ischemia show changes in the mitochondria and ER compatible with the experimental picture of hypoxia: i.e., dilated ER, with loss of ribosomes, swelling of mitochondria and the appearance of flocculent densities in the mitochondria. Tissues taken from the patients who had experienced repeated episodes of shock, whom we designated as those in "chronic shock," showed changes paralleling the acute changes, but also showed much evidence of autophagocytosis as a) the cells attempted to achieve a lower metabolic requirement in order to survive, and b) they attempted to "clean-up" and remove altered and damaged organelles and debris from previous bouts with sublethal ischemic injury. We hope that the increased knowledge of tissue and cellular injury obtained by the immediate autopsy will provide a means of integration, hypothesis formation and testing of the vast knowledge of cell biology and pathology, and the opportunity for developing in the human the potential for testing new hypotheses in model systems resulting in immediate and innovative feedback for the patient in terms of diagnosis, functional monitoring and treatment.