Flash-induced oxygen evolution in the thylakoids of plants and algae exhibits damped oscillations with period four. These are well described by the S-state model of Kok et al. [Kok, B., Forbush, B. & McGloin, M. (1970) Photochem. Photobiol. 11, 457-475], with damping provided by empirical misses and double hits in the reaction center of photosystem II. Here we apply a mechanistic interpretation of misses as mainly determined by reaction centers that are inactive at the time of the flash due to the presence of either P+ or QA, according to the electron transfer equilibria on the donor and acceptor sides of the reaction center. Calculation of misses on this basis, using known or estimated values of the equilibrium constants for electron transfer between the S states and tyrosine Yz, between Yz and P680, as well as between the acceptor plastoquinones, allows a natural description of the flash number dependence of oxygen evolution. The calculated misses are different for each flash-induced reaction center transition. Identification of this mechanism underlying the miss factor for each transition leads to the recognition of two different reaction sequence cycles of photosystem II, with different transition probabilities, producing an intrinsic heterogeneity of photosystem II activity.