To clarify the mechanism of the effect of the dopaminergic antagonist, metoclopramide, on orthostatic hypotension (OH) associated with diabetes mellitus, 24 diabetics with OH and 7 diabetics without OH were kept standing for 15 min. after an injection of 2ml saline (S-injection) and then, on the following day, for 15 min. after intravenous administration of 10 mg metoclopramide (M-administration). Blood pressure (BP) and pulse rate (P) were measured throughout the study. Plasma renin activity (PRA), aldosterone concentration (PAC), norepinephrine (PNE) and epinephrine (PE) were determined at 0 and 15 min.<BR>(1) In 15 of the diabetics with OH, after upright posture following M-administration, orthostatic hypotension improved and P increased, especially in 10 patients, PNE and PAC increased significantly (p<0.05), and PRA showed a fairly good elevation compared with the results obtained after S-injection. In addition, these patients had milder diabetic complications or obesity.<BR>(2) In the remaining 9 patients with OH, after upright posture following M-administration, there was no improvement in OH and no increase in P. Moreover, PRA and PNE showed only a slight increase, whereas PAC was elevated considerably compared with the results after S-injection. The patients also had severe diabetic complications or emaciation.<BR>(3) There was no significant difference in PE after S-injection or M-administration in all patients.<BR>(4) In 10 of the 15 diabetics with improvement of OH, PRA, PAC, PNE and PE, especially PRA and PNE following M-administration were significantly (p<0.05) higher than those of diabetics, in whom the OH did not improve.<BR>(5) In diabetics without OH, there were no significant differences in BP and P after S-injection or M-administration, and PNE following M-administration increased significantly (p<0.05) compared with results obtained for diabetics, in whom the OH improved.<BR>In conclusion, the improvement of OH caused by metoclopramide is probably related to milder diabetic complications or obesity, and the mechanism can be explained by increases in plasma renin, aldosterone, norepinephrine and epinephrine, especially renin and norepinephrine, and also by the enhancement of sensitivity of the blood vessels to catecholamines.