Caveolae are Ω-shaped invaginations of the plasma membrane containing a variety of proteins that have been suggested to participate in the orchestration of many signal transduction events including that of mechanosensitisation. For example, it has recently been reported that cultured HeLa cells respond to hypo-osmotic swelling by rapid (5 mins) disassembly of caveolae and membrane ‘flattening’ (Sinha et al (2011)). Resistance artery smooth muscle cells have abundant caveolae (Tong et al (2009)) and are highly mechanosensitive. This myogenic reactivity is commonly evinced as an initial dilation to an elevation in intralumenal pressure followed by an active vasoconstrictive response to return the vessel towards its initial diameter. It is physiologically important in maintaining tissue blood flow and minimising pre-capillary blood pressure surges. The purpose of this study was to determine if the morphological appearance of caveolae in vascular smooth muscle cells of resistance arteries, in situ, were altered in response to physiological mechanical stress, i.e. an increase in intravascular pressure. Uterine artery segments dissected from 3 month old C57BL mice were mounted in a pressure myograph (physiological salt solution, 5%CO2-air, 37°C) for continuous monitoring of diameter. Intravascular pressure was initially set at 60mmHg and arteries allowed to equilibrate for 60 mins (diameter=156.2(±15.3)μm, mean(±SEM), n=10) before being exposed to physiological mechanical stress by increasing the intravascular pressure to 120mmHg. This caused vasodilation with a peak of +0.19 (±0.04)-fold change in diameter from 60mmHg. Subsequent myogenic contraction constricted vessel diameters to less than that (-0.13 (±0.05)-fold change c.f. to 60mmHg) previously observed at 60mmHg. Arterial segments in three conditions (i) resting 60mmHg intravascular pressure, (ii) 120mmHg intravascular pressure at peak dilation, (iii) 120mmHg intravascular pressure with myogenic contraction, were fixed within 1-2 seconds and processed for electron microscopic examination of caveolae. In each condition 3-5 segments (two sections of each) were examined. Figure 1 shows one electron micrograph of vascular smooth muscle cells from each of the three conditions. In each, rows of caveolae could be observed along the length of the plasma membrane of the vascular smooth muscle cells. There was no evidence of flattening of the caveolae structure in any sections examined. These results indicate that the integrity of caveolae is retained in vascular smooth muscle cells exposed to an acute, physiological mechanical stress. In addition to data from non-vascular smooth muscle (Gabella and Blundell (1978)), these results suggest that caveolae morphology can be retained during physiological mechanosensitisation.