Due to the high mortality associated with pulmonary interstitial emphysema in the low-birth-weight infant, a method was developed to predict the infants most at risk for death. This information will allow the discriminant selection of patients for future trials of an alternative method of mechanical ventilation, highfrequency ventilation. During a 3-year-period (July 1, 1979 through June 30, 1982), 70 infants were retrospectively analyzed to determine the clinical parameters important in predicting mortality. The infants at highest risk for death included those of younger gestational age, those with birth weight less than 1,500 g (95% of all mortalities), and those that developed pulmonary interstitial emphysema within the first 24 hours of life. Mortality sharply increased in the infants with birth weight less than 1,500 g whose ventilatory requirements exceeded a peak inspiratory pressure of 25 cm H2O on day 1. Morbidity was high in the survivors as evidenced by a 54% incidence of bronchopulmonary dysplasia. With multivariant analysis, it was possible to isolate the variables (birth weight and highest peak inspiratory pressure on day 1) most influential in predicting mortality and to construct a formula for predicting mortality in the infants with birth weight less than 1,500 g. With a subsequent prospective study of 30 infants, the predictive accuracy of the formula was established.