Chlorothiazide, an orally effective diuretic agent, was given intravenously to pentobarital anesthetized mongrel dogs in a prime dose of 20 mg/kg, followed by a 30-minute infusion of 20 mg/kg. Control dogs received glucose infusion. Blood pressure responses to 0.005 and 0.1 ug norepinephrine, 0.05 [mu]g epinephrine, and 0.05 [mu]g isopropylnorepi-nephrine were elicited before and after infusion. Chlorothiazide decreased significantly the blood pressure rise due to norepinephrine and epinephrine and decreased the hypotensive response to isopropyl-norepinephrine. These results suggest that this compound may induce some refractoriness to agents tending to alter the state of contraction of vascular smooth muscle.