Prooxidants induce release of Ca2+ from mitochondria through the giant solute pore in the mitochondrial inner membrane. However, under appropriate conditions prooxidants can induce Ca2+ release without inducing a nonspecific permeability change. Prooxidant-induced release of Ca2+ is selective. Presumably, this is the result of the operation of a permeability pathway for H+ coupled to the reversal of the Ca2+ uniporter, the latter generating the selectivity. The solute pore and prooxidant-induced Ca2+-specific pathways exhibit common sensitivities to a set of inhibitors and activators. It is proposed that the pore can operate in two open states: (1) permeable to H+ only and (2) permeable to solutes of M(r) < 1500. Under some conditions, prooxidants induce the H+-selective state which, in turn, collapses the inner membrane potential and permits selective loss of Ca2+ via the Ca2+ uniporter.