4-Hydrazino-1,2,3-benzothiadiazine-1,1 dioxide hydrochloride (EX 4211A) and 6-chloro-3,4-dihydro-3-( β -oxo- n -propyl)-7-sulfamyl-2H-1,2,4-benzothiadiazine 1,1-dioxide phthalazone azine (EX 5004) were studied in the rat and dog to elucidate the mechanism(s) by which these compounds produced hypotensive effects. EX 4211A and EX 5004 were potent hypotensive agents in the anesthetized rat, mildly hypotensive in the anesthetized normotensive dog, and produced a moderate degree of hypotension in unanesthetized renal hypertensive dogs. EX 5004 and EX 4211A appeared to produce their hypotensive effect by the lowering of peripheral resistance through a direct action on vascular smooth muscle.