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When exposed to heat stress, increases in cutaneous blood flow and sweating in well-healed grafted skin are severely attenuated, which could impair whole-body heat loss if skin grafts cover a large portion of total body surface area (TBSA). It is unknown to what extent whole-body heat loss is impaired when skin grafts cover a significant (eg, >50%) proportion of TBSA. The authors examined whole-body heat exchange during and after 60 min of cycling exercise in the heat (35°C; 25% relative humidity), at a fixed rate of metabolic heat production (~400 W) in a woman (age, 36 years; mass, 78.2 kg) with well-healed (17+ years) skin grafts covering 75% of TBSA. Her responses were compared with two noninjured control subjects. Whole-body evaporative and dry heat exchange were measured by direct calorimetry. While exercising in the same ambient conditions and at the same rate of heat production, relative evaporative heat loss of nongrafted skin in the grafted subject (ie, evaporative heat loss per m2) was nearly twice that of the control subjects. However, total rate of evaporative heat loss reached only 59% of the amount required for heat balance in the skin-grafted subject compared with 92 ± 3% in controls. Thus, the increase in core temperature was 2-fold greater for the grafted (1.22°C) vs control (0.61 ± 0.19°C) individuals. This case study demonstrates that a large area of grafted skin greatly diminishes maximum evaporative heat loss during exercise in the heat, making a compensable environment for control subjects uncompensable for skin-grafted individuals.