Apoptosis plays a key role in the steady state of continuously renewing tissues. The goal of this study was to determine whether apoptosis was a mode of hair cell loss in mammalian inner ear sensory epithelia. Hair cell loss was induced by systemic treatment with the ototoxic aminoglycoside antibiotic gentamicin in guinea pig. The vestibular sensory epithelia were examined at different times after administration via semi-thin and thin sections in situ labeling by the terminal deoxynucleotidyl transferase catalysis of digoxigenin tagged nucleotides to the free 3'-OH ends of fragmented DNA. Apoptotic labeling was detected 3-7 days after treatment. The majority of the apoptotic nuclei was found adjacent to the luminal surface. Analysis of semi-thin and thin sections revealed two modes of hair cell degeneration: (1) Apoptosis within the epithelium, showing typical morphological changes of condensation and fragmentation of the nucleus and modifications of cytoplasmic organelles. (2) Swelling of the cell, vacuolation and distortion of cell shape, and extrusion into the lumen. The results indicated that vestibular hair cells undergo apoptosis after ototoxic traumas.