A damped oscillatory state of swelling under conditions of energized ion transport in EDTA-treated rat liver mitochondria is described. The period of oscillation is dependent upon pH and temperature, and the oscillatory state requires: (a) EDTA and high pH, which are related to an effect of divalent cations; Mg ++, Ca ++, and Sr ++ inhibit the oscillatory state but not swelling under steady-state conditions; (b) an energy source; either electron flow through various segments of the respiratory chain, or ATP is effective; (c) a permeant anion; lithium and sodium salts of anions like acetate, propionate, or phosphate are most effective; (d) appropriate conditions of osmolarity; and (e) for initiation either substrate, ATP, permeant anion, or O 2. After a train of 2–3 oscillations has faded away, oscillations can be reinitiated by O 2, ATP, or permeant anion. Oscillations in mitochondrial swelling are paralleled by changes in electron and energy transfer parameters. The shrinkage phase is associated with increased respiration, a more highly oxidized state of pyridine nucleotides, a stimulation of ATP hydrolysis, an inhibition of proton production, and stimulation of cation production. When the swelling phase reoccurs, these changes are reversed and show evidence of damping. It is concluded that the oscillatory states of electron and energy transfer pathways may be under the control of mitochondrial swelling and ion transport by a feedback mechanism.