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1. Experiments were done on mature foetal lambs, 135-145 days in gestation, exteriorized at Caesarean section, and on new-born lambs aged 12-60 hr. In the foetal lambs, test substances were added to lung liquid and then spontaneous ventilation was induced or the lungs were statically inflated with gas or saline. In the new-born lambs, the left lung was ventilated in order to maintain respiratory gas-exchange, while foetal lung liquid, taken from previous experiments and containing test substances, was introduced into the right lung, which was then inflated with gas and used for permeability measurements. In both foetuses and new-borns, the gas used was O2 or N2O and, at 20 min intervals, ventilation or static inflation was interrupted, the gas in the lungs absorbed into the circulation and the remaining liquid sampled through the trachea. The following test substances were used in various combinations: [14C]-erythritol, [3H]sucrose, [14C]inulin, [131I]albumin, and the polymer [131I]-PVP. The last of these was separated, after the experiments, by gel filtration with Sephadex G200 or G50, into fractions of defined molecular radius. [131I]albumin, or a large molecule fraction of [131I]PVP, was used as a volume marker. 2. Spontaneous ventilation was associated with the absorption of liquid and with an alteration in the foetal pattern of non-electrolyte permeability that could be characterized by postulating an opening up of water-filled cylindrical pores to 34-56 A in radium. In the new-born lambs, the results suggested pores 7-14 A in radius. 3. Static inflation of the foetal lungs with gas, to pressures of 25-35 cmH2O, gave permeabilities appropriate for pores 5-5-12 A in radius. Static inflation with gas, to pressures of 41-49 cmH2O, produced changes appropriate for much larger channels, more than 125 A in radius and possibly much larger. With one exception, expansion with saline produced changes similar to those obtained by gas inflation to 25-35 cmH20. 4. It was concluded that in the initial stages of pulmonary ventilation a change takes place in alveolar epithelial cells. The increase in size would be sufficient to allow for rapid liquid absorption, but is not so great as to permit significant penetration by plasma albumin. The results obtained in the lung of the new-born lamb statically inflated to 25-32 cmH2O suggest that, following the initial adaptation, alveolar permeability returns towards the foetal pattern, although the pores remain larger than in the foetus. The change in permeability pattern at birth appears to depend on the degree of lung expansion with gas.

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