The present study attempts detection of some substances that aggravate the lung tissue after cardiopulmonary bypass (CPB). A rabbit lung basement membrane was used as a substrate for this experiment. We found that human plasma contained more than two substances that degraded lung basement membrane substrate (LBMS). One was acid protease, active at pH 3 to 4, and the other was a substance (or substances) active within a physiologic range with an optimum pH of 8 to 9. This was thought to be biologically significant. The substance(s) that degraded the lung basement membrane substrate at an alkaline range had a low molecular weight of less than 10,000 and was suppressed in the presence of plasma constituents having a molecular weight of 10,000 to 30,000. The basement membrane degrading substance(s) could not be identified. During CPB, the activity of the substance(s) increased, whereas the level of cathepsin D and the trypsin inhibitory capacity decreased. However, after termination of surgery, the activity of the substance(s) definitely decreased, whereas the level of cathepsin D and trypsin inhibitory capacity increased linearly. The possibility may exist that lung basement membrane destruction in humans can be attributed to the alkaline-active substance(s) passing through the bronchial vessels during bypass surgery, which could evoke interstitial edema, hemorrhage, and finally atelectasis.