As multiple trauma is ubiquitous, affects predominantly young people and is attended by a high mortality, it seemed a fruitful area for study in an effort to reduce morbidity and mortality. One of the main problems in trauma research has been accurate description of the severity of injury and associating severity with subsequent outcome. While a number of scoring systems have been proposed the Injury Severity Score has been the most widely adopted and validated. The Injury Severity score was adopted with a number of other systems of scoring infection and other complications in a retrospective study of multiple trauma patients admitted to an Intensive Therapy Unit. This study revealed an unexpected increased in mortality in the latter two years of the study period which was not associated with an increase in injury severity as assessed by the ISS nor by any other change in patient characteristics which might explain this finding. Eventually it was noted that the introduction of a hypnotic drug etomidate for use in sedation of ventilated patients seemed to be associated with the increased mortality. Clinical evidence suggested that etomidate might inhibit adrenocortical function and an experimental study indeed confirmed that etomidate had a direct effect on adrenal steroidogenesis such that cortisol and aldosterone production were completely suppressed. Following analysis of the retrospective clinical study etomidate was withdrawn from use in our unit. Analysis of mortality rates both for trauma patients and the general patient population indicated a reversion to the rate which pertained prior to introduction of etomidate. The results of retrospective and prospective clinical studies strongly implied that the administration of etomidate was associated with an increased mortality among trauma patients. The experimental study based on clinical observations clearly demonstrated that etomidate infusion was a potent inhibitor of adrenal steroidogenesis. It seems highly likely that the detrimental effect of etomidate was mediated by its direct inhibitory effect on the production of cortisol and aldosterone by the adrenal gland. Subsequent clinical and experimental studies from other authors tend to confirm these findings.