The effect of salicylate, the active metabolite of aspirin (acetyl salicylic acid) in the presence of Ca 2 + and phosphate on mitochondrial permeability transition (MPT) was studied. MPT is often associated with opening of a Ca 2 + -induced pore. The opening of this pore leads to swelling, loss of mitochondrial membrane potential and release of accumulated Ca 2 + . In freshly isolated rat kidney mitochondria, salicylate (400 μM) in the presence of 20 nmol Ca 2 + /mg protein and 0.1 mM phosphate induced swelling, loss of mitochondrial membrane potential and release of accumulated Ca 2 + . All these changes were eliminated when cyclosporin A (1 μM), (a pore inhibitory agent) was included in the incubation medium. Unlike salicylate, unhydrolyzed aspirin (400 μM) induced these changes slightly. We concluded that salicylate acts as an activator of Ca 2 + and phosphate in promoting the opening of kidney inner mitochondrial membrane pore. As a result a great consideration should be given to its toxicological effect.