Rat liver mitochondria were exposed to extramitochondrial free calcium between 0 and 5 microM and/or 5 minutes of anoxia followed by 10 minutes of reoxygenation. At concentrations higher than 4 microM, the membrane potential collapsed indicating the permeability transition of the mitochondrial membrane. Anoxia-reoxygenation shifted this transition to lower calcium concentrations. Anoxia-reoxygenation alone resulted in the decrease of ADP stimulated respiration down to about 40% of its initial value. Between 1 and 2 microM, a protective effect in terms of respiration and oxidative protein modification was found. It is concluded that calcium may suppress the formation of reactive oxygen species during anoxia-reoxygenation before permeability transition occurs.