Prior to apoptotic body formation, cells quickly exhibit the apoptotic volume decrease (AVD) in response to stimulation with a death receptor- or mitochondrion-mediated apoptosis inducer. The AVD induction preceded cytochrome c release, caspase activation, DNA laddering and cell death. Pan-caspase blockers failed to abolish the AVD induction. Anion channel blockers abolished the AVD induction and prevented apoptotic biochemical events and cell death. Apoptosis inducers rapidly activated outwardly rectifying Cl− currents that were sensitive to osmotic shrinkage. Thus, it is concluded that activation of volume-sensitive anion channels is involved in the AVD induction which is an early prerequisite to apoptosis. Necrotic cells exhibit persistent swelling until cell rupture. Lactacidosis causes the necrotic volume increase (NVI) and cell death in brain neurons and glial cells. In cultured neuronal and glial cells, lactacidosis in fact induced persistent swelling without following volume regulation. Volume-regulatory anion channels were inactivated by lactacidosis. When lactacidosis-resistant anion channels were introduced by applying the VacA toxin, glial cells exhibited volume regulation after transient swelling under lactacidosis conditions. Pretreatment of glial cells with VacA suppressed necrotic cell death after a lactacidosis insult. Thus, it is concluded that inhibition of volume-sensitive anion channel is involved in lactacidosis-induced NVI and necrotic death in glial cells. [Jpn J Physiol 54 Suppl:S28 (2004)]