The possible occurrence of lung damage if alveolar units are allowed to collapse and reopen breath by breath during mechanical ventilation with normal tidal volumes was investigated. Anaesthetised, paralysed, open chest rabbits were subjected to either intrathoracic negative (NEEP; n = 6) or positive (PEEP; n = 6) end-expiratory pressure during volume controlled mechanical ventilation. Both experimental settings were preceded by a 30 min control period and followed by a 30 min recovery period during which a PEEP of 0.2 kPa was maintained. Pao2 and pulmonary compliance deteriorated significantly in the NEEP group during the experimental period and compared to ventilation with PEEP. Partial restoration of lung mechanics and blood gases was achieved during the recovery period. After an alveolar recruitment manoeuvre, this recovery was complete. Lung clearance studied by depositing an aerosol of technetium-99m-labelled diethylenetriamine pentaacetate (99mTc-DTPA) in the alveoli, was significantly faster during ventilation with NEEP compared to the PEEP group (P = 0.0002) as well as the control period (P = 0.0029). It did not recover completely during the recovery period but remained significantly faster. Light microscopic histology was normal in both groups with no evidence of inflammation or epithelial disruption. We conclude that previously healthy rabbit lungs show only a transient disturbance of lung mechanics and blood gases with repetitive collapse and re-expansion. The integrity of the alveolar microstructure is preserved. The disturbance in the alveolo-capillary permeability persists and may indicate surfactant related alveolo-capillary barrier dysfunction.