Acute effects of piretanide, a loop diuretic, on blood pressure (BP) and urinary output as well as long-term effects on serum electrolytes were compared in conscious spontaneously hypertensive rats (SHR) to that of hydrochlorothiazide (HCT) both given alone and in combination with the converting enzyme (CE) inhibitor ramipril. There were no acute or chronic falls in BP with low doses of either diuretic. Ramipril at a dose of 10 mg/kg normalized BP, which was accompanied by initial natriuresis and, over the long term, K+ preservation. Minimally effective doses of piretanide but not HCT given in combination with 1 mg/kg ramipril produced a greater fall in BP both acutely and chronically than ramipril alone at unaltered K+ preservation. To match this fall in BP with HCT, large doses were required, which caused hemoconcentration and impaired K+ preservation.