Perfluorocarbon (PFC) compounds induce pulmonary hyperinflation and respiratory distress in some animals following intravenous administration. This study was designed to quantify the effects of two PFC emulsions on lung volumes and compliance and to identify the mechanism of pulmonary hyperinflation. New Zealand White rabbits received isotonic saline (3 ml/kg), Fluosol (15 ml/kg) or Oxygent (90% perfluorooctyl-bromide emulsion, 3 ml/kg). After seven days we measured functional residual capacity, vital capacity, lung compliance and thoracic gas volume. Gross and microscopic histologic examination of the lungs was performed. Functional residual capacity after Fluosol administration was 16.0 +/- 4.0 ml/kg, significantly greater than after saline (3.4 +/- 1.0 ml/kg) or Oxygent (4.0 +/- 1.4 ml/kg). Vital capacity was lower with Fluosol (30 +/- 5.0 ml/kg) than after saline (37 +/- 3.0 ml/kg) or Oxygent (37 +/- 2.0 ml/kg). Thoracic gas volume increased from 9 +/- 1.0 ml/kg (saline) to 16 +/- 13 ml/kg (Oxygent) and 33 +/- 7.0 ml/kg (Fluosol). Lung compliance was the same after saline (1.6 +/- 0.5 ml.cm H2O-1.kg-1) and Oxygent (1.5 +/- 0.3 ml.cm H2O-1.kg-1) but lower after Fluosol (0.9 +/- 0.1 ml.cm H2O-1.kg-1). Gross pathology demonstrated foam exudation from airways of animals receiving PFCs and intra-alveolar foam was identified by light microscopy. These results show intra-airway foam formation causes gas trapping and shifts tidal breathing to a less compliant region of the pressure-volume curve.