Treatment of developing rats with thyroid hormone results in accelerated maturation of sympathetic and adrenal medullary responses to reflex activation of central sympathetic outflow. In this study, we examined the effects of neonatal hyperthyroidism on the responsiveness of the sympathetic nervous system of adult rats to acute stress. Hyperthyroidism was produced in Long-Evans hooded rats by injections of thyroxine (neo-T4, 1 mg/kg body wt) on postnatal days 1-4. Littermate controls received injections of vehicle only. In adulthood, male rats of the two groups were prepared with chronic tail artery catheters to allow repeated sampling of blood and direct measurements of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats/min). Two days after surgery, rats were stressed by exposure to 1 min of inescapable foot shock (2.0 mA, 0.6-s duration, every 6 s). The activity of the sympathetic nervous system was assessed by measuring plasma levels of norepinephrine (NE) and epinephrine (E). Basal plasma levels of NE and E and resting MAP did not differ between neo-T4 and control rats. However, basal HR was elevated in neo-T4 rats. Footshock-induced increments in plasma levels of both catecholamines were greater in neo-T4 compared with control rats even though behavioral responses to footshock were similar across groups. However, neo-T4 rats were more active when tested in an open field on each of 3 consecutive days. These findings indicate that neonatal treatment with T4 results in hyperresponsiveness of the sympathoadrenal medullary system to acute stress that persists into adulthood.