Publisher Summary This chapter discusses central cholinergic mechanisms in the thermoregulation of the rat. If rats, during brief hexobarbitone anaesthesia, are intravenously injected with barely sublethal doses of organo-phosphorus cholinesterase inhibitors that are able to pass the blood-brain barrier, the animals produce hypothermia of 4-6º in 2-3 hours, followed by spontaneous recovery in 12-20 hours. The anticholinesterase hypothermia in the rat can partly be prevented by systemic atropine, but not by atropine methyl nitrate. Hypothermia is caused by a combination of increased heat loss and reduced heat production. As to heat loss, the anticholinesterases appear to shift the set point for heat release (SPHR) of the hypothalamic thermostat to a lower level. This makes the rat use its facilities for releasing heat until the body temperature has again become lower than the new SPHR. The lowered set point can be restored to the normal level by intracerebroventricular (i.c.v.) application of atropine. Intraventricular injection of carbachol produces a hypothermia that is similar to that following anticholinesterase administration, but is markedly shorter in duration and can be repeated in one rat every 1 or 2 hours. It appears that under suitable experimental conditions the animals produce no vasodilatation following an i.c.v. carbachol injection. This occurs when, because of theprolonged inactivity in a cool environment, the body temperature goes down sufficiently before the carbachol is given. The phenomenon is independent of the activity of the striated muscles and the respiration since deep curarization of the rats had no effect.