It is shown that Ca(2+)-dependent activation of respiration of liver mitochondria from hibernating ground squirrels is accompanied by mitochondrial swelling. 2. The swelling of mitochondria from hibernating ground squirrels, as well as the activation of mitochondrial respiration, is precluded by cyclosporin A, p-bromphenacylbromide and oligomycin. Carboxyatractiloside, on the contrary, under these conditions favors the swelling and the acceleration of respiration. 3. It was concluded that Ca(2+)-dependent activation of hibernating ground squirrel liver mitochondrial respiration resulted from the appearance of a non-specific permeability pathway and from swelling of mitochondria.