AbstractExposure to radio-frequency energy (RFE) of millimeter wavelengths results in a relatively high skin-heating rate, with only a moderate rate of core heating. Yet, prolonged RFE exposure eventuates in severe hypotension and death. In this study, we characterized pathophysiological changes associated with prolonged RFE sufficient to induce hypotension.Anesthetized rats were exposed to 35-GHz RFE with a power density of 75 mW/cmUsing infrared thermography, we confirmed a relatively high temperature (>46 °C) at the skin surface of the irradiated site. Histopathological results included hemorrhage and congestion of blood vessels in the dermis and subcutis of irradiated skin without induction of burn. As in environmental heating, significantly greater levels of serum glucose, creatinine, uric acid, and anion gap were observed in rats exposed to longer-duration RFE (approx. 38-min exposures) than in shorter-duration (approx. 19-min exposures) or sham (time control) animals. However, changes in blood electrolytes or liver enzymes (often seen during heatstroke) were not observed after the RFE exposures. Even without major tissue injury or serum/plasma enzyme and electrolyte changes, rapid cutaneous heating via RFE induced profound hypotension that eventuated in death.