OBJECTIVE/HYPOTHESIS: Hair cells of the mammalian auditory system do not regenerate, and therefore their loss leads to irreversible hearing loss. Aminoglycosides, among other substances, can irreversibly damage hair cells. Somatostatin, a peptide with hormone/neurotransmitter properties, has neuroprotective effects by binding to its receptor. In this study, we tested whether somatostatin can protect hair cells from gentamicin-induced damage in vitro. STUDY DESIGN: This study confirmed the expression of somatostatin receptor mRNA within the cochlea and analyzed the effect of somatostatin on gentamicin-induced hair cell damage and death in vitro. METHODS: Expression of somatostatin receptor mRNA in the rat cochlea was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Protection of auditory hair cells from gentamicin was tested using two different concentrations (1 microM and 5 microM, respectively) of somatostatin. RESULTS: We detected somatostatin receptor-1 and -2 mRNA and in the organ of Corti (OC), spiral ganglion, and stria vascularis by RT-PCR. Moreover, we could see significantly less hair cell loss in the OCs that were pretreated with either 1 microM or 5 microM of somatostatin as compared with samples treated with gentamicin alone. CONCLUSIONS: Decreased hair cell loss in somatostatin-treated samples that had been exposed to gentamicin provides evidence for a protective effect of somatostatin in aminoglycoside-induced hair cell death in vitro.