Plasma microvescicles, particles ranging from 100-1000µm in diameter produced by cells through blebbing of the cell membrane, have been implicated in disease processes (1), angiogenesis (2) and activation of endothelial progenitor cells (3). Microvesicles have not been studied beyond quantification of their plasma abundance in the venous circulation and questions remain regarding their abundance in arterial blood, uptake and release by tissues, and whether physiological stimuli lead to their production. The aim of the current study was to determine the impact of whole body heat stress, which markedly increases limb and systemic blood flow, on the exchange of total and platelet derived microvesicles across the lower extremities of healthy humans. METHODS: Six young healthy men (27±7 years, 182±7 cm, 74±8 kg) were instrumented with radial artery and common femoral venous catheters. Citrated venous and arterial blood samples were drawn simultaneously, without stasis to limit platelets activation at rest. Participants then underwent whole-body passive heating using a water perfused suit until skin and core temperature rose 6 and 1°C (heating duration: 46±8 min). Samples were serially centrifuged to render them acellular and platelet poor. Samples were pelleted and labelled with bodipy-maleimide and FITC conjugated CD41 antibodies to enumerate total phospholipid and platelet derived microvesicles, respectively using imaging flow cytometry. Comparisons were made using ANOVA or dependent t-tests as appropriate. All values are mean ± SEM. At baseline, microvesicles were more abundant in arterial than venous blood (1169±208 vs. 714±139 per µl whole blood, p<0.02), reflecting an uptake across the lower limb. Passive heat stress did not increase microvesicle uptake across the limb (6.5 x 107 ± 3.2 x 107 vs. 37.8 x 107± 18.4 x 107 microvesicles/min-1, p=0.17), despite a 2-3 fold increase in limb plasma flow (p<0.01). CD41+ microvesicles concentrations were similar in arterial and venous samples (p=0.90) and unaltered with passive heat stress (p=0.82). The net flux of platelet microvesicles was also unaffected by passive heat stress (p=0.36). DISCUSSION: These data show for the first time an uptake of microvesicles at rest and following heat stress in the limbs of healthy humans. However, moderate heat stress does not seem to alter platelets derived microvesicle abundance and suggests little uptake or release. The rate of uptake of phospholipid positive microvesicles may be increased by passive heating in this healthy population however a larger cohort is required to confirm this trend. Microvesicle flux may relate to shear stress, with the creation or inhibition of uptake occurring arterially and the low shear stresses of the microcirculation and venous system facilitating uptake.