Hypotension is a common problem in patients on hemodialysis. To further investigate this problem, the number of platelet α2-adrenoceptors and the activity of lymphomonocyte β2-adrenoceptors were measured in 10 hemodialyzed patients with normal blood pressure and in 10 sex- and age-matched persistently hypotensive hemodialyzed patients. Density of α2-adrenoceptors was assessed by the specific binding of 3H-yohimbine to intact platelets, while the function of β2-adrenoceptors was estimated by the production of cAMP after the exposure of lymphomonocytes to isoprenaline. The maximal number of α2-adrenoceptors was increased in the hypotensive compared to the normotensive group (262.13 vs. 77.21 fmol/mg protein; p < 0.01). Plasma norepinephrine was higher in the hypotensive than in the normotensive uremic patients (640 ± 195 vs. 344 ± 156 pg/ml; p < 0.01). Plasma epinephrine did not differ in the two groups (90 ± 30 vs. 94 ± 24 pg/ml). The amount of cAMP, produced by stimulation of lymphomonocytes, was lower in the hypotensive than that in the normotensive uremic patients (7.7 ± 2.4 vs. 15.6 ± 5.4 pmol/106 cells; p < 0.002). The increased number of α2-adrenoceptors together with a high level of norepinephrine and reduced activity of adenylate cyclase (coupled with β2-adrenoceptors) support the hypothesis that hypotension in the hemodialyzed uremic patients may be related to a defect in adrenoceptor couplin