Hypoglycemia induces physiological changes that influence thermoregulatory mechanisms. We studied such responses in a group of healthy males (mean age 23.5 yr, body mass index 23.7 kg/m2) during hyperinsulinemic euglycemia (E; 4.5 mmol/l) and hypoglycemia (H; 2.5 mmol/l) and under placebo control conditions (P; saline). Plasma epinephrine (P < 0.0001) and norepinephrine (P < 0.01) levels increased during H and were unchanged during P and E. During H, early increases in metabolic rate (P < 0.05), forearm blood flow (P < 0.01), and sweating (P < 0.01) were followed by a fall in skin temperature (from -1.2 to -2.6 degrees C) and blood flow (P < 0.01). Core temperature fell after 40 min of H and continued to fall thereafter (-0.34 +/- 0.08 degrees C). E and P had minimal effect on skin temperature and blood flow. In summary, in healthy human subjects, H causes a fall in core temperature by heat dissipation at the skin surface through evaporative heat loss and conduction of heat to the periphery, despite an increase in metabolic heat production.