There are various difficulties studying macromolecular systems. One on these is that the applicable theoretical and experimental methodologies often have significant limitations. A common solution is to use smaller "model" compounds; study them in detail; and extrapolate these results to the larger system. Although very useful, this raises the question, how accurate is the extrapolation? In the present Letter we want to give an example related to activation energies, which have large importance describing fragmentation processes. There are diverse methods determining activation energies in mass spectrometry; many values obtained this way can be found in the literature. However, most of these relate to small molecules. Available methods for studying compounds over ca. 200 Da size are less accurate; and there are few reliable values. "Common wisdom" suggests that, for the same reaction type, increasing the molecular size should decrease the barrier height (i.e. the critical energy, but not the internal energy needed for fragmentation!): Increasing size typically stabilizes the product ion (and product radical, if any) with respect to the parent compound. With the advance of experimental techniques to study macromolecules, it may become useful to be able to estimate, how molecular size influences the activation energy.