We applied a new ventilator-multi-plethysmograph system to evaluate the effect of surfactant replacement in newborn rabbits under well controlled, nearly physiological conditions characterized by normal ECG and adequate PCO2 in right ventricular heart blood obtained at the end of the experiment. Up to 10 animals were ventilated in parallel with a pressure-constant common respirator system. Using a working pressure of 4.9 kPa (50 cmH2O), we could adjust the pressure delivered to each animal within the range of 0.49-4.4 kPa (5-45 cmH2O), by changing the length of an open high-resistance tube constituting the outflow limb of the connection between the common ventilator tube and the tracheal cannula. Immature newborn animals obtained after 27.5 days gestation and ventilated for 30 min with a tidal volume of 8-10 ml.kg-1 had a mean +/- SD lung-thorax compliance of 4.2 +/- 1.1 ml.kPa-1.kg-1 (0.41 +/- 0.11 ml.cmH2O-1.kg-1) and PCO2 of 8.5 +/- 1.9 kPa. In littermates treated at birth with a large dose of natural surfactant (Curosurf, 200 mg.kg-1, compliance increased to 6.0 +/- 1.0 ml.kPa-1.kg-1 (0.68 +/- 0.10 ml.cmH2O-1.kg-1) (p less than 0.01) and PCO2 decreased to 6.9 +/- 1.2 kPa (p less than 0.01). Near-term animals, obtained at 30 days gestation and ventilated under similar conditions had a compliance of 7.2 +/- 0.9 ml.kPa-1.kg-1 (0.71 +/- 0.09 ml.cmH2O-1.kg-1) and PCO2 of 6.4 (1.2) kPa. Administration of surfactant (same dose as above) to these mature animals at birth had no adverse effects.