Cardiac output (CO), arterial blood pressure (ABP), heart rate (HR), blood gases and blood flow (BF) to the brain, heart, kidney and skeletal muscles and other cephalic tissues in five dogs were studied before and at 30 minutes of betahistine infusion (0.12 to 0.2 mg per minute per kilogram). The particle distribution method using radioactive labeledl41Ce (15 %) and85Sr (15 %) microspheres was utilized to quantitate and assess BF and CO. In the five dogs, the increase in CO averaged 20.8%, ABP remained constant, and HR increased in all but one exception where it decreased slightly concomitant with a decrease in Paco2. Brain BF increased (+ 29.6%) in the dogs whose Paco2remained constant. The BF increased to the heart (25.4%) and skeletal muscle (80%), while BF to the kidney and other tissues did not change. The change in HR appears to account for the change in CO. The dilating effect of betahistine on blood vessels, in the skeletal muscle, brain and heart could reduce peripheral resistance and decrease ABP. Thus, the increase in HR may be mediated through baroreceptor mechanisms rather than by a direct effect of betahistine. In addition, a decrease in Paco2is more effective for decreasing cerebral BF than betahistine is for increasing blood flow.