Orthostatic hypotension is a serious problem in patients with diabetes mellitus (DM) undergoing hemodialysis (HD). To evaluate cerebral circulation during orthostasis in patients with DM, we examined changes in mean blood flow velocity in the middle cerebral artery (VMCA) during 60 degrees head-up tilt for 5 minutes in patients with DM (six men, two women; age, 57 +/- 3 years [mean +/- SEM]; HD duration, 47 +/- 27 months) before and after bicarbonate HD by using transcranial Doppler sonography. The findings were compared with those in HD patients without diabetes (non-DM; 12 men, 5 women; age, 47 +/- 3 years; HD duration, 82 +/- 23 months). Mean blood pressure (MBP) in the supine position, hematocrit (Hct), plasma fibrinogen, and volume of fluid removed by HD were not significantly different between the two groups (MBP, 106 +/- 6 versus 103 +/- 4 mm Hg; Hct, 26% +/- 1% versus 28% +/- 1%; fibrinogen, 355 +/- 37 versus 357 +/- 27 mg/dL; fluid, 2.5 +/- 0.2 versus 2.3 +/- 0.2 L). Percentage of change in VMCA (% VMCA) during tilt was compared between the groups before and after HD. Before HD, MBP decreased significantly to 93 +/- 5 mm Hg during tilt only in patients with DM. The degree of MBP reduction was -13 +/- 2 mm Hg in DM and -2 +/- 2 mm Hg in non-DM patients (P < 0.01). % VMCA equally decreased during tilt; DM, -12% +/- 3%, and non-DM, -12% +/- 2%. After HD; MBP decreased by 36 +/- 7 mm Hg in patients with DM, which was significantly greater than before HD. VMCA also decreased in both groups after HD, and % VMCA in DM (-32% +/- 5%) was significantly greater than before HD (P < 0.01) and in non-DM patients (-13% +/- 2%; P < 0.01). % VMCA positively correlated with the percentage of change ratio of MBP during tilt in both groups after HD (DM, r = 0. 87, P < 0.01; non-DM, r = 0.61, P < 0.01). Our results showed a significant decrease in cerebral blood flow velocity during tilt of equal magnitude in both groups before HD despite differences in the level of hypotension, whereas reduction in cerebral blood flow velocity and decrease in MBP were more marked in DM after HD. Orthostasis could thus cause hemodynamically mediated brain damage after HD, especially in patients with DM.