The involvement of free oxygen radicals in ischemia-reperfusion injury is generally accepted. We describe here the loss of efficiency of reticular membranes to sequester Ca2+ due to free oxygen radical damage in vitro. Based on experimental results we suggest that the primary effect of free oxygen radicals is alteration of the lipid component of the membrane manifested in the increase of passive Ca2+ leak. Prolonged treatment of microsomes with free oxygen radical generating systems also led to the decrease of Ca(2+)-ATPase activity which is caused as we suppose by modulation of the lipid-Ca2+ pump interactions. A protective effect of butylated hydroxytoluene on the depression in the Ca2+ uptake and Ca(2+)-ATPase activities supports our suggestions.