Occupational injuries are common among firefighters who perform strenuous physical exertion in extreme heat. The thermal protective clothing (TPC) worn by firefighters inhibits normal thermoregulation, placing the firefighter at risk of hypohydration and hyperthermia that may result in cognitive decline. We tested whether cognitive function changes after treadmill exercise in TPC. In an initial study (Cog 1), ten healthy volunteers performed up to 50 min of treadmill exercise while wearing TPC in a heated room. A battery of neurocognitive tests evaluating short-term memory, sustained and divided attention, and reaction time was administered immediately before and after exercise. In a follow-up study (Cog 2), 19 healthy volunteers performed a similar exercise protocol with the battery of cognitive tests administered pre-exercise, immediately post-exercise, and serially up to 120 min after exercise. Subjects performed 46.4 ± 4.6 and 48.1 ± 3.6 min of exercise in the Cog 1 and Cog 2, respectively. In both studies heart rate approached age predicted maximum, body mass was reduced 1.0-1.5 kg, and body core temperature increased to levels similar to what is seen after fire suppression. Neurocognitive test scores did not change immediately after exercise. Recall on a memory test was reduced 60 and 120 min after exercise. The mean of the 10 slowest reaction times increased in the 120 min after exercise. Fifty minutes of treadmill exercise in TPC resulted in near maximal physiologic strain but alterations in neurocognitive performance were not noted until an hour or more following exercise in TPC.