The effects of single and repeated combinations of gentamicin and sound on Preyer reflex and cochlear hair cells in pigmented guinea pigs have been examined. Gentamicin at 50 mg/kg for 10 days and an 8 kHz pure tone (116 dB for 60 min) cause little or no hair cell loss when given alone. In combination, hair cell loss occurs with the gentamicin and sound acting synergistically. If the pure tone is given on the first of a 10-day gentamicin course there is considerable loss of hair cells in the basal coil; if given on the 10th day the loss is several times less. Repeating the treatments after 3 weeks increases the hair cell loss and the synergistic effect. A possible explanation for the differential synergistic effect is discussed.