A critical aspect to understanding the molecular basis of Alzheimer's disease (AD) is the characterization of the kinetics of interconversion between the different species present during amyloid-beta protein (A beta) aggregation. By monitoring hydrogen/deuterium exchange in A beta fibrils using electrospray ionization mass spectrometry, we demonstrate that the A beta molecules comprising the fibril continuously dissociate and reassociate, resulting in molecular recycling within the fibril population. Investigations on A beta 40 and A beta 42 amyloid fibrils reveal that molecules making up A beta 40 fibrils recycle to a much greater extent than those of A beta 42. By examining factors that could influence molecular recycling and by running simulations, we show that the rate constant for dissociation of molecules from the fibril (k(off)) is much greater for A beta 40 than that for A beta 42. Importantly, the k(off) values obtained for A beta 40 and A beta 42 reveal that recycling occurs on biologically relevant time scales. These results have implications for understanding the role of A beta fibrils in neurotoxicity and for designing therapeutic strategies against AD.