Cu(II) and Fe(III) addition to isolated rat liver mitochondria produced inhibition of mitochondrial respiration. Decreased mitochondrial respiration is maximal in O2 consumption in active state 3. Mitochondrial respiratory dysfunction is related to phospholipid peroxidation in mitochondria supplemented with Cu(II) and Fe(III). Different response to metal addition indicates different intracellular toxicity mechanisms. The direct impact on the organelle functionality of far lower concentrations of Cu than Fe suggests a dissociating event in the mechanism of toxicity of both metals.