We present the characteristic features of mineralocorticoid receptor regulation in human mononuclear leukocytes in patients with diabetes mellitus. Eighteen diabetic patients (3M and 15F, aged from 28 to 77 years with a mean of 53±14 (mean±sd) years) and 7 normal subjects (6M and IF, aged from 29 to 59 years with a mean of 41±13 years) were studied. The mean plasma aldosterone concentration in the diabetic patients was significantly lower than that in the normal subjects (137±62 vs 189±36 pmol/l, p<0.05). Seven of the 18 diabetic patients were hypoaldosteronemic. These 7 patients, however, showed normokalemia, except one with mild hyperpotassemia. The number of binding sites of [3H]aldosterone to mineralocorticoid receptor in the diabetic patients was significantly higher than that in the normal subjects (853±281 vs 488±109 sites/cell, p<0.05), but there was no significant difference in Kd of [3H]aldosterone binding to mineralocorticoid receptor between the diabetic patients and normal subjects (1.34±0.37 vs 0.99±0.61 nmol/l). In the diabetic patients, a significant negative correlation was observed (r=0.70, p<0.01) between plasma aldosterone concentration and the binding sites, but not between plasma aldosterone concentration and Kd. In the total subjects, including normal subjects and diabetic patients, a significant negative correlation was also found between plasma aldosterone concentration and binding sites (r=0.72, p<0.001). These results suggest that increased binding sites of mineralocorticoid receptor may help to prevent diabetic patients from being hyperkalemic.