It has been suggested that the family of natriuretic peptides (NP) has a protective role in volume overloading. Specific binding sites for atrial natriuretic peptide (ANP) and the kidney analog urodilatin (URO) were identified and quantified with computerized autoradiography and biochemical assay in the cryosection in the cochlear and vestibular (utricle/ampulla) tissue. Immunohistochemistry was used to identify and localize NP-like immunoreactive cells. Different levels of specific receptors between and within the inner ear compartments were detected. The presence of specific receptors for NP, as well as unequal distribution of NP-immunoreactivity between the compartments (in certain parts of the cochlea and the endolymphatic sac), may indicate a local autocrine and/or paracrine action of these peptide systems (presumably as a result of the integration of the different peptide effects), independent of their action via the more conventional systemic route, in addition to differences in response of the inner ear compartments to the load. The present results on specific binding of ANP and URO in the inner ear tissue may suggest physiological homology between the inner ear and the kidney. Moreover, a similar role of NP in these organs is suggested.