This study is intended to measure the effect of shock on the heart and to investigate the cardiotoxic properties of circulating factors produced during the shock state. It forms part of a larger group study of experimental and clinical shock. The work is presented in two parts. Part one comprises studies in experimental shock. Groups of greyhounds have been subjected to haemorrhagic hypotension with varying modifications. Using a reservoir model, in which hypoxaemia is prevented by controlled ventilation, it is possible to maintain haemodynamic parameters at pre-shock values by colloid replacement for up to four hours following three and one-half hours of hypotension and retransfusion. These dogs, however, demonstrate a defect in myocardial oxygen usage indicating damage to the heart following prolonged hypotension. A bioassay system is described for measuring the level of myocardial depressant factor (M.D.F.) in circulating blood. This factor has been described and investigated by Lefer (1974) and previous work has correlated its appearance with the development of heart failure following experimental haemorrhagic shock (Lefer et al, 1966) and with the depression of myocardial contractility in the normal animal (Glenn and Lefer, 19 71b). This study demonstrates a correlation of M.D.F. levels with the appearance of a metabolic defect in oxygen usage by the heart. The two phenomena appear as the shock period is prelonged beyond one hour and are not affected by the abolition of the haemorrhagic enteritis of canine shock by pretreatment with an "elemental" diet or enterectomy prior to shock. ?-sympathetic blockage, however, reduces the level of M.D.F. without altering myocardial oxygen usage and suggests that other factors are also involved. Studies have been carried out to assess the role of myocardial hypoxia in shock. The efficacy of indirect methods (Huckabee, 1961; Gudbjarnason and Bing, 1962) for the measurement of anaerobic metabolism are assessed in the anoxic heart. While all these methods indicate that glycolysis occurs in the acutely anoxic heart, none of the parameters indicate that myocardial anaerobic metabolism occurs during or after experimental shock. Purification of plasma samples by gel chromatography has been carried out and demonstrates that M.D.F. activity appears to be associated with a group of compounds of molecular weight 500 - 600 in contrast to the range 800 - 1,000 described by others (Lefer and Martin, 1970a; Okuda et al, 1973). In view of the criticism and contradictory evidence of Wangensteen and his colleagues (Wangensteen et al, 1973a and b) further studies have been carried out to demonstrate that M.D.F. is not an artefact of the bioassay or purification technique. The observed depression is not related to electrolyte changes during plasma purification or contamination of the chromatographic peaks by chloride. Part two consists of a clinical study of patients who had developed shock from various causes and a group of control patients who had not been shocked. A rise in M.D.F. level in the plasma is associated with an episode of shock and significantly higher levels of M.D.F. are found in patients who do not survive the shock state. Many of these patients have evidence of heart failure. Purification of these samples reveals similarities with the peaks found in canine haemorrhagic shock but it is not possible to correlate the "in vitro" depression in clinical shock with a specific molecular weight range. Study of a large group of shocked patients shows that cardiac failure is a common finding in many types of shock and thus further study of circulating M.D.F. may be important in the investigation of the pathology of shock and in the development of a successful therapeutic approach to the management of the shocked patient.