A group of 36 patients with severe adult respiratory distress syndrome (ARDS) meeting previously established blood gas criteria (mortality rate 90%) became candidates for possible extracorporeal respiratory support [low frequency positive pressure ventilation with extracorporeal CO2 removal (LFPPV-ECCO2R)]. Before connecting the patients to bypass we first switched the patients from conventional mechanical ventilation with positive end expiratory pressure (PEEP) to pressure controlled inverted ratio ventilation (PC-IRV), and then when feasible, to spontaneous breathing with continuous positive airways pressure (CPAP). Forty eight hours after the patients had entered the treatment protocol, only 19 out of the 36 patients in fact required LFPPV-ECCO2R, while 5 were still on PC-IRV, and 12 were on CPAP. The overall mortality rate of the entire population was 23%. The only predictive value of success or failure of a particular treatment mode was total static lung compliance (TSLC). No patients with a TSLC lower than 25 ml (cm H2O)-1 tolerated either PC-IRV or CPAP, while all patients with a TSLC higher than 30 ml (cm H2O)-1 were successfully treated with CPAP. Borderline patients (TSLC between 25 and 30 ml (cm H2O)-1) had to be treated with PC-IRV for more than 48 h, or were then placed on LFPPV-ECCO2R if Paco2 rose prohibitively. We conclude that TSLC is a most useful measurement in deciding on the best management of patients with severe ARDS, unresponsive to conventional treatment.