The purpose of this study was to determine the actions of several pharmacological agents on the circulatory system, and more specifically on the superior mesenteric vascular bed, in response to environmental heat stress in chloralose-anesthetized rats. Animals were instrumented with Doppler flow probes on the mesenteric and renal arteries and exposed to an ambient temperature of 40 degrees C. Heart rate, mean arterial blood pressure (MAP), and core (Tc) and tail skin temperatures were also monitored. As Tc progressively increased from 37 degrees C during heat exposure, MAP rose to a plateau and then fell precipitously as Tc exceeded 41.5 degrees C. Mesenteric resistance increased throughout the early stages of heating before sharply declining prior to the reduction in MAP. The pressor and mesenteric resistance responses to constant infusions of several adrenergic agonists after MAP began falling (Tc = 41.3 degrees C) were significantly (P less than 0.05) attenuated compared with infusions into normothermic animals. In a second set of experiments, injections of both norepinephrine and angiotensin II were made 30 min before and approximately 10, 30, 50, 70, and 90 min after initiation of heating. These injections increased both MAP and mesenteric resistance; however, at TcS greater than 40 degrees C, the responses to both agonists were progressively and significantly attenuated. In a final group of animals, barium chloride infusions produced similar pressor and regional resistance changes during both normothermia and severe hyperthermia (Tc greater than 42 degrees C). These results indicate that, in the chloralose-anesthetized rat, hyperthermia disrupts adrenoceptor function but does not alter the intrinsic ability of vascular smooth muscle to contract.