SummaryAn emphysema-like lesion was produced in rats by the periodic administration of papain aerosol. Functional residual capacity (FRC) was measured at the completion of the papain treatments and at two week intervals during the next month. Progesterone (5 mg/kg sc) daily for one month after development of the papain lesion, caused a significant decrease in FRC values; untreated control emphysematous rats maintained elevated values. Measurements of (a) average intraalveolar distance (mean linear intercept) and (b) air spaces in histological sections prepared from the lungs of rats sacrificed at the end of the papain treatment period and rats sacrificed 4 weeks later, after progesterone therapy, also suggested a therapeutically beneficial effect by the hormone. In vitro, progesterone had no effect on casein hydrolysis by papain.