OBJECTIVE Ventilatory strategies combining low tidal volume (V(T)) with positive end-expiratory pressure (PEEP) are considered to be lung protective. The influence of the PEEP level was investigated on bacteriology and histology in a model of ventilator-associated pneumonia. METHODS Nineteen New Zealand rabbits. METHODS The animals were mechanically ventilated with a positive inspiratory pressure of 15 cmH(2)O and received either a zero end-expiratory pressure (ZEEP, n=6), a 5 cmH(2)O PEEP (n=5) or a 10 cmH(2)O PEEP (n=4). An inoculum of Enterobacter aerogenes was then instilled intrabronchially. The non-ventilated pneumonia group (n=4) was composed of spontaneously breathing animals which received the same inoculum. Pneumonia was assessed 24 h later. RESULTS The lung bacterial burden was higher in mechanically ventilated animals compared with spontaneously breathing animals. All animals from the latter group had negative spleen cultures. The spleen bacterial concentration was found to be lower in the 5 cmH(2)O PEEP group when compared to the ZEEP and 10 cmH(2)O PEEP groups (3.1+/-1.5 vs 4.9+/-1.1 and 5.0+/-1.3 log(10) cfu/g, respectively; p<0.05). Lung weight and histological score values were lower in the spontaneously breathing animals as well as in the 5 cmH(2)O PEEP group compared with the ZEEP and 10 cmH(2)O groups. CONCLUSIONS Mechanical ventilation substantially increased the lung bacterial burden and worsened the histological aspects of pneumonia in this rabbit model. Variations in terms of lung injury and systemic spreading of infection were noted with respect to the ventilatory strategy.