In the first series of experiments, the effects of administration of insulin (0.04-0.12 IU/microliter) into the preoptic anterior hypothalamic area on thermoregulatory responses were assessed in unanesthetized rats at various ambient temperatures (Ta). Intrahypothalamic administration of insulin induced a dose-dependent rise in rectal temperature. At Ta = 8 degrees C, the hyperthermia in response to insulin was due to increased metabolism, whereas at Ta = 30 degrees C, the hyperthermia was due to cutaneous vasoconstriction. However, at Ta = 22 degrees C, the insulin-induced hyperthermia was due to both increased metabolism and cutaneous vasoconstriction. In the second series of experiments, the effects of intracerebroventricular administration of insulin on 35 hypothalamic units classified as cold-responsive, warm-responsive, or thermally unresponsive were assessed in 35 rats anesthetized with urethane. It was found that the majority (80%) of the warm-responsive units were depressed by insulin, whereas the majority (70%) of the cold-responsive units were excited by insulin. The data indicate that insulin acts on the hypothalamic thermally responsive neurons to induce hyperthermia by promoting an increase in heat production and/or vasoconstriction.