The distribution and location of atrial natriuretic peptides (ANP) in the middle ear mucosa (MEM) of guinea pigs were studied with immunocytochemistry (avidin-biotin-peroxidase complex method) and immuno-electron microscopy. A great quantity of ANP-immunoreactive (ANP-IR) cells, including oval small cells and irregular large cells, was observed in the tissue of the MEM. The strong ANP-IR product was observed in the inner membrane of the partial capillary walls. Under immuno-electron microscopy, the ANP-IR product was found to be spheres of 250 to 350 nm in diameter. The results of this study suggest that the MEM has the function of secreting ANP. This paper provides the morphological basis for the study of ANP's function in the MEM.