Tetrodotoxin (10 pmol in 300 nl of Ringer), injected bilaterally into the region of the amygdala in conscious rabbits, virtually abolished the sudden falls in ear pinna blood flow that normally occur in response to salient environmental stimuli (touching the animal's fur, slightly moving its cage, or applying or removing a drape covering the cage). Time spent at 0-20% of maximum flow values during a 10 min observation period, commencing 15 min after injection of tetrodotoxin, significantly decreased compared with the pre-injection control period (30+/-14 s compared with 286+/-24 s, P<0.01, n=8 rabbits) and the time spent at 70-100% of maximum flow values significantly increased (521+/-36 s compared with 127+/-29 s, P<0.01). Vehicle was injected on the day before tetrodotoxin injections in four of eight rabbits and on the day after tetrodotoxin injections in the other four rabbits, in a counterbalanced design. Rabbits fully recovered from the effects of tetrodotoxin in one day. Vehicle did not significantly affect the time spent at different flow percentage values. Falls in ear blood flow elicited by noxious stimuli (ear pinch, inhalation of formaldehyde vapor) occurred in a normal pattern after tetrodotoxin. Amygdaloid circuitry is thus necessary for the production of falls in ear pinna blood flow that occur in response to unconditioned non-noxious stimuli, but not for the falls that occur in response to unconditioned noxious stimuli in rabbits. In humans, the amygdaloid region may also be involved in co-ordinating falls in cutaneous blood flow occurring in response to salient or anxiety-evoking stimuli. Thus, discovery of the neural pathways by which amygdaloid circuitry alters ear pinna blood flow in rabbits may elucidate the manner in which similar cardiovascular changes occur in humans during anxiety reactions.