Stimulation of the internal ear by a sound or an acceleration evokes an electrical response in hair cells, the ear's sensory receptors. In many auditory organs , each hair cell's response is highly sensitive to the frequency of stimulation as a result of electrical tuning mediated by ion channels in the cell's membrane. Ion channels are also involved in the release of synaptic transmitter that excites nerve fibers, which in turn, carry information into the brain. The prominence of ion channels in both signalling processes motivates the proposed investigations of the structures and function of such channels in hair cells. Hair cells are highly specialized cells endowed with unique organelles for the capture of stimulus energy and for the control of synaptic transmitter release. Unfortunately, the small number of hair cells in an ear greatly impedes the study of the proteins that constitute these organelles and account for their unique properties. Making use of the tools of molecular biology, the proposed experiments involve the identification of genes uniquely expressed in hair cells, as well as those active only in supporting cells. This approach should provide a better understanding of the proteins that account for the hair cell's specialized properties. Hair cells of the human internal ear are damaged by numerous genetic conditions, infections, loud sounds, ototoxic drugs, and aging. Until recently, there was no evidence that the receptor cells lost as a result of such processes could be replaced. During the past decade, however, several research groups have demonstrated hair cell regeneration in the ears of birds and even mammals. The proposed studies of early stages in the internal ear's development should indicate which chemical factors are of importance in the decision to create new hair cells and in each hair cell's maturation. More specifically, crucial chemical messengers will be identified by use of viruses to interfere with their normal functions. Hair cells are probably maintained by exposure to growth factors supplied by other cell types. Similar techniques will additionally show which factors are of particular importance in this context. These studies should provide information useful in promoting the survival, repair, and eventual replacement of hair cells in the human internal ear.