Three classes of inner mitochondrial membrane (IMM) channel activities have been defined by direct measurement of conductance levels in membranes with patch clamp techniques in 150 mM KCl. The "107 pS activity" is slightly anion selective and voltage dependent (open with matrix positive potentials). "Multiple conductance channel" (MCC) activity includes several levels from about 40 to over 1000 pS and can be activated by voltage or Ca2+. MCC may be responsible for the Ca(2+)-induced permeability transition observed with mitochondrial suspensions. A "low conductance channel" (LCC) is activated by alkaline pH and inhibited by Mg2+. LCC has a unit conductance of about 15 pS and may correspond to the inner membrane anion channel, IMAC, which was proposed from the results obtained from suspension studies. All of the IMM channels defined thus far appear to be highly regulated and have a low open probability under physiological conditions. A summary of what is known about IMM channel regulation and pharmacology is presented and possible physiological roles of these channels are discussed.