Cyclotron phase locking arises when two ion clouds have similar mass-to-charge ratios and a sufficiently large ion population such that the relative cyclotron dynamics are dominated by the mutual Coulomb E x B drift dynamics. Once two or more ion clouds are phase locked, a Fourier transform ion cyclotron resonance mass spectrometer cannot distinguish them by image current detection since the ion clouds have identical detected cyclotron frequencies. A simple analytical model, based on the assumption of rigid ion clouds, predicts that the maximum number of ions having equal charge states and closely spaced masses, which can be contained in two clouds before phase locking occurs, is proportional to their mass difference and to the square of the magnetic field strength divided by the molecular mass, Δm(B/M) 2 , and is independent of the charge state. This molecular mass dependence establishes an upper molecular mass limit for resolving closely spaced peaks due to cyclotron phase locking. The rigid ion cloud model, supported by numerical simulations, demonstrates that phase locking causes the 1 Da spacing of the isotopic envelope for large molecules to be unresolvable past a high molecular mass limit (M max ). M max is directly proportional to B and independent of the charge state for adjacent ion clouds with equal charge state. An order of magnitude estimate predicts that M max 1x10 4 (in units of Da and Tesla), independent of charge state for peaks having a 1 Da spacing. This estimate concurs with present instrumental capabilities. Full three-dimensional numerical stimulations on realistic ion clouds, which include the combined effects of internal and external ion cloud dynamics, Z-oscillation, linear dipolar excitation and trap potential anharmonicity, demonstrate the qualitative validity of the assumptions inherent in the rigid ion cloud model predictions.