The surface concentration versus surface pressure relationship of 39 proteins under dynamic adsorption conditions at the air−water interface has been studied. It was found that the slope of these plots, ϑ (in ergs/mg), which is defined as surface activity, showed a positive correlation (r = 0.86) with the adiabatic compressibility of the proteins. The linear regression line passed almost through the origin, suggesting that, theoretically, rigid and inflexible globular proteins would not be able to reduce the surface tension of water even at a saturated monolayer coverage. Some empirical equations were derived for the estimation of the ϑ values of unknown proteins on the basis of their amino acid compositions as well as secondary structure contents. The compressibility values predicted from these calculated ϑ values agreed with the experimental values. The experimental ϑ values of globular proteins also showed a negative linear correlation (r = 0.77) with the ΔG° of thermal unfolding of the proteins. The results of this study indicated that the surface activity of globular proteins is intimately related to their molecular flexibility and their susceptibility to conformational changes at the interface. A direct correlation exists between the thermal stability and the interfacial stability of globular proteins.