Atrial natriuretic hormone (ANH) levels in plasma and the right atrium of non-obese diabetic mice in the decompensated diabetic state were investigated by radioimmunoassay and histological examination. Severely diabetic mice, with blood glucose levels over 33.6 mmol/l showed significantly higher hematocrit, plasma sodium and calculated plasma osmolarity than the age-matched normoglycemic mice. The plasma ANH levels in diabetic mice were significantly lower (17.5 pmol/l) than those in normoglycemic mice (43.6 pmol/l). The ANH concentrations in the right atrium were 26.6 mg/g protein in the diabetic and 11.2 mg/g protein in the normoglycemic mice. The right atrium in the diabetic mice showed much wider immunohistochemical staining by anti-human ANH antiserum compared with the normoglycemic mice. An increase in the number of atrial specific granules in the diabetic mice was observed by transmission and scanning electron microscopy. Morphometrical analysis indicated that the number of granules increased to more than twice that in the normoglycemic mice. These findings indicate that plasma ANH decreases in diabetic mice. The store of right atrial ANH may be increased to compensate for the marked dehydration in severe diabetes.