Atrial natriuretic peptide (ANP) levels in cardiocytes and plasma were examined by using immunohistochemistry, electron microscopy, and radioimmunoassay in non-obese diabetic mice (NOD). Cardiocyte ANP mRNA expression was measured by the polymerase chain reaction method. ANP immunoreactivity in the auricular cardiocytes was more prominent in hyperglycemic mice (NOD-h) than in normoglycemic mice (NOD-n). Ultrastructural examination showed that auricular cardiocytes of the NOD-h group contained more cytoplasmic granules than cells of the NOD-n group. Ultrastructural morphometry indicated that the number of granules per auricular cardiocyte was significantly larger in the NOD-h group than in the NOD-n group (P less than 0.01), whereas the granule diameter was significantly smaller in the NOD-h group (P less than 0.01). Radioimmunoassay showed that ANP levels in the NOD-h auricular cardiocytes were significantly higher than those in the NOD-n cardiocytes (P less than 0.01); the opposite was true in plasma. Cardiocyte ANP mRNA expression was lower in the NOD-h group than in the NOD-n group.