It has been proposed that endotoxin contributes to the development of multiple organ failure (MOF) in acute pancreatitis. Endotoxaemia is transient and may not be detected by intermittent blood sampling. By contrast, not only can changes in the patient's endogenous antiendotoxin core antibody pool persist for many days, but depletion of this pool may be a key event in determining the physiological significance of endotoxaemia. A series of 33 patients with acute pancreatitis had daily measurement of Acute Physiology Score (APS) and levels of C-reactive protein, interleukin 6, endotoxin, immunoglobulin (Ig) G and IgM antiendotoxin core antibodies, and prospective documentation of complications. Endotoxin was detected in the serum of 13 patients, while a significant change in levels of endogenous antiendotoxin core antibodies was detected in all those with severe pancreatitis and in 28 overall. MOF developed in seven patients, five of whom died. The combination of a rising APS over the first 48 h of admission and a significant fall in endogenous IgG antibody level was observed in all patients who developed MOF (seven of seven), but in only one of 16 without MOF (P = 0·00003; overall predictive value 91 per cent). This study suggests that measuring the initial trend in APS and the concentration of endogenous IgG antiendotoxin core antibody provides a means of identifying patients with acute severe pancreatitis who are at high risk of developing MOF. This group might benefit from passive immunotherapy with antiendotoxin antibodies.