Poikilothermia, the inability to maintain a constant core temperature independent of ambient temperature, markedly influences both the mental and physical function of affected patients; furthermore, prolonged hypothermia can induce numerous complications. To establish the pathophysiology of thermoregulation underlying poikilothermia in man, we compared 4 women with acquired poikilothermia, with 9 female control subjects. The activity of the main thermoregulatory effector mechanisms was assessed in a thermoneutral environment, and during subsequent cold stress and heat exposure. At thermoneutrality the patients had a significantly lower rectal temperature and resting metabolic rate compared with the controls; no patient showed peripheral vasoconstriction or shivering. Cooling revealed markedly reduced peripheral vasoconstriction in 3 patients and failure of the metabolic response in 2 patients; unlike controls, no patient exhibited shivering. Heat challenge revealed severely reduced capacity for heat dissipation in all patients. We conclude that in patients with poikilothermia, the mechanisms for both heat conservation and heat dissipation are seriously attenuated. Careful monitoring of the core temperature and adequate measures to maintain normothermia are of great importance in patients with poikilothermia in order to provide adequate treatment, improve the quality of life, and prevent serious complications.