The role of renal alpha 2-adrenoceptors in the regulation of glomerular filtration and renal perfusion is unknown. We studied the effects of alpha 2-adrenergic blockade on renal hemodynamics in six patients with insulin-dependent diabetes mellitus (IDDM) and in six healthy subjects. At the basal state, glomerular filtration rate (GFR) was higher in IDDM although the difference from control levels was not statistically significant. Volume expansion, achieved by infusion of isotonic sodium chloride solution, during placebo infusion induced a significant drop in GFR in healthy subjects but not in IDDM patients. Infusion of the alpha 2-adrenoceptor antagonist idazoxan did not further modify the effect of volume expansion on GFR. Renal plasma and blood flow as well as filtration fraction were not significantly changed by volume expansion or idazoxan infusion. Plasma renin activity and plasma aldosterone levels decreased during volume expansion in both IDDM and control subjects. In conclusion, volume expansion induced decreased GFR in healthy controls but not in IDDM patients. Since infusion of idazoxan did not affect GFR or other parameters of renal hemodynamics, renal alpha 2-adrenoceptors do not seem to be involved in the regulation of renal function. Hence, enhanced renal alpha 2-adrenoceptor activity is not likely to underlie hyperfiltration as seen in IDDM.