Overt forearm pain can be experienced by the crews of high performance military aircraft during manoeuvring. The pain could be associated with a hydrostatic rise in forearm vascular transmural pressure and an increase in forearm blood flow, which has been observed following exposure to vascular transmural pressures of 150mmHg and above (Greenfield & Patterson, 1954). To test the hypothesis that high-G arm pain is related to a rise in forearm blood flow, the relationship between vascular transmural pressure, forearm vascular resistance and pain was examined. Following approval by the RAF Experimental Medicine Ethics Committee, eight healthy male volunteers (mean ± S.D.; age 33.3 ± 9.3 years) were studied in accordance with local guidelines and the Declaration of Helsinki. Subjects placed one arm through a port in a hypobaric chamber, and forearm vascular transmural pressure was elevated by a series of 1 minute hypobaric exposures, at incrementing differential pressures of 40, 80, 120, 140, 160 and 200mmHg with 2 min at 0mmHg between exposures. The sequence was repeated after a 30 min rest interval. Forearm venous pressure (FVP) was measured by indwelling catheter in the median antecubital vein, and blood velocity in the proximal axillary artery was monitored by 2D and Doppler ultrasound imaging. Forearm vascular resistance was assessed by Doppler resistive index (RI), which is defined as (S–D)/S, where S is the systolic velocity waveform peak, and D is the end-diastolic trough. Pain rating was recorded by visual analog scale. Data are presented as means ± S.E.M., and compared using the Wilcoxon signed rank test (for pain scores) and paired t tests (for vascular transmural pressure). A linear relationship between FVP and pain was observed (r²=0.8, n=35). In all subjects, a change from the normal high resistance type flow pattern of the axillary artery occurred at high FVP (176mmHg ± 7.7mmHg). The flow pattern changed to that of a low resistance vascular circuit, with flow in diastole, such that RI fell to a value of less than 1. This was associated with an increase in pain rating (P<0.001) from 5.4 ± 0.7 in the exposure preceding the change to 8.4 ± 0.5. In the second series of exposures, there was a fall in the transmural pressure at which this phenomenon was observed (P<0.01), to a mean FVP of 135.4mmHg ± 11.2mmHg. The observed fall in RI suggests a profound reduction in vascular resistance occurs at high vascular transmural pressure in the forearm, which is associated with the development of severe pain. Repeated exposure reduces the transmural pressure at which this effect occurs.