In 12 patients requiring therapy with mechanical ventilation for acute respiratory failure, total static compliance (Cst) increased from 29 +/- 4 ml/cm H2O at a tidal volume (TV) of 5 ml/kg to 42 +/- 7 ml/cm H2O at a TV of 15 ml/kg. Similarly, Cst increased from 42 +/- 7 ml/cm H2O to 52 +/- 8 ml/cm H2O between 0 and 6 cm H2O of positive end-expiratory pressure (PEEP). At high levels of pulmonary inflation (ie, high PEEP and large TV) compliance decreased. The changes of total respiratory compliance with TV were mainly due to changes in pulmonary compliance. With PEEP, the functional residual capacity increased, and specific compliance did not change. Two mechanisms may be responsible for the changes in compliance. First, varying TV or PEEP will alter the position of tidal ventilation on the pressure-volume curve, resulting in an increase in compliance with increasing TV and PEEP up to a point, where overdistention occurs and compliance decreases. Secondly, the function of the surface-lowering substance may be altered in acute pulmonary parenchymal disease, thus disturbing the regulation of surface tension over the range of pulmonary inflation studied.