The present authors hypothesised that in severe acute respiratory distress syndrome (ARDS), pronation may reduce ventilator-induced overall stress (i.e. transpulmonary pressure (P(L))) and strain of lung parenchyma (i.e. tidal volume (V(T))/end-expiratory lung volume (EELV) ratio), which constitute major ventilator-induced lung injury determinants. The authors sought to determine whether potential pronation benefits are maintained in post-prone semirecumbent (SR(PP)) posture under pressure-volume curve-dependent optimisation of positive end-expiratory pressure (PEEP). A total of 10 anesthetised/paralysed, mechanically ventilated (V(T) = 9.0+/-0.9 mL.kg(-1) predicted body weight; flow = 0.91+/-0.04 L.s(-1); PEEP = 9.4+/-1.3 cmH(2)O) patients with early/severe ARDS were studied in pre-prone semirecumbent (SR(BAS)), prone, and SR(PP) positions. Partitioned respiratory mechanics were determined during iso-flow (0.91 L.s(-1)) experiments (V(T) varied within 0.2-1.0 L), along with haemodynamics, gas exchange, and EELV. Compared with SR(BAS), pronation/SR(PP) resulted in reduced peak/plateau P(L) at V(T)s> or =0.6 L; static lung elastance and additional lung resistance decreased and chest wall elastance (in prone position) increased; EELV increased (23-33%); V(T)/EELV decreased (27-33%); arterial oxygen tension/inspiratory oxygen fraction and arterial carbon dioxide tension improved (21-43/10-14%, respectively), and shunt fraction/physiological dead space decreased (21-50/20-47%, respectively). In early/severe acute respiratory distress syndrome, pronation under positive end-expiratory pressure optimisation may reduce ventilator-induced lung injury risk. Pronation benefits may be maintained in post-prone semirecumbent position.