Carbon monoxide uptake is a sensitive measure of lung injury, but its application to mice using the rebreathing technique has produced a nonlinear dependence of carbon monoxide uptake on mouse weight, in contrast to the linear relationship obtained in larger rodents using the single-breath technique. Improvements were made to the equipment and the procedures used in the rebreathing technique which resulted in linear relationships between uptake and weight in three mouse strains, CBA/J, C57BL/6J, and C57L/J. Sequential measurements were made on mice during the early and intermediate phases after irradiation of the thorax which demonstrated the development of injury in individual mice with considerable sensitivity. Estimates of the proportion of lung which was considered to be nonfunctional based on its histological appearance were obtained using alveolar ducts as sampling markers in 64 C57L/J mice between 10 and 31 weeks after irradiation. The deficit in carbon monoxide uptake was determined on the day of sacrifice for each mouse, and the results showed good correspondence to the histological estimate of the extent of damage. The correspondence between breathing rate elevation and the histological assay was not as good.

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