The unimolecular decomposition of large polyatomic hydrocarbon (720 and 1000 modes) and protein (540 modes) molecules and molecular ions is investigated by applying RRKM, effective RRK (ERRK), and Arrhenius models. It is found that the calculated values of the RRKM unimolecular rate coefficients, k(E), agree well with fragmentation lifetimes of molecular ions in a mass spectrometer. Calculations of the effective number of modes at a given temperature and excitation energy together with ERRK expression for k(E) yield values which are similar to those calculated by RRKM. With the assumption that a 1000-mode supermolecule is its own heat bath at a vibrational temperature commensurate with its total internal energy, an Arrhenius expression for the rate coefficient is obtained which yield values for the rate coefficient which are in a rough agreement with values calculated by the two methods described above.