A low [Hb] (Hb concentration) is out-balanced by peripheral vasodilation via mechanisms that are incompletely understood. Peripheral vasodilation is influenced by NO (nitric oxide) released from vascular endothelium in response to increased vessel wall shear stress, and absorption by Hb is the main mechanism by which the bioactivity of NO is disarmed. Thus we propose that graded NO absorption is the mechanism through which a low [Hb] is related to peripheral vasodilation. In the present study, we examined the relationship between [Hb] and FMD (flow-mediated vasodilation; 5 min of cuff ischaemia) of the radial and brachial arteries in 33 normal subjects and in 13 patients with Type II diabetes, known to have impaired NO-mediated vasodilation. The smaller radial artery provided the more sensitive test, as it had a 2-fold larger FMD than the brachial artery (22+/-18% compared with 9+/-18% respectively, in normal subjects; means+/-S.D., P<0.05). FMD of the radial artery had a negative correlation with [Hb] (r(2)=-0.66, P<0.05; n=27). In subjects with [Hb] below and above the median of 14.1 g/dl, the radial artery FMD was 30+/-22% compared with 13+/-12% respectively (P<0.05). In diabetic patients, FMD was lower and a co-variation with [Hb] could not be established. Thus, in normal subjects, NO-mediated endothelium-related vasodilation at least partly out-balanced the 'added burden' of a low [Hb] during post-ischaemic reperfusion.