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Equilibrium sedimentation centrifugation in Percoll density gradient reveals the density fluctuation during the cell cycle in the defective vacuolar morphology mutants of Saccharomyces cerevisiae. During the cell cycle, the vacuole, which is the biggest intracellular compartment, shows morphological changes that are not responsible for the cyclic density fluctuation. The growth phase determines the buoyant density of S. cerevisiae. The density fluctuation during the cell cycle may be due to the periodical formation and breakdown of macromolecules.