1. The effects of two groups of diuretics on renin secretion have been compared in dogs anaesthetized with pentobarbital.
2. Frusemide, ethacrynic acid and bumetanide cause an immediate rise in renin secretion which is not inhibited either by dl-propranolol or by a bilateral ureterovenous anastomosis which prevents salt and water loss.
3. Clopamide, metolazone and indapamide do not cause an immediate rise in renin secretion. Renin hypersecretion is induced only 1 h after intravenous injection of these diuretics.
4. Renin secretion was studied for 6 h after frusemide injection: the immediate rise was followed by a later increase in renin secretion. This later rise was inhibited by propranolol and by ureterovenous anastomosis.
5. These results allow us to distinguish between a direct renal mechanism responsible for early renin hypersecretion, which appears to be connected with the action of the diuretic on the ascending limb of Henle's loop, and an indirect mechanism responsible for late renin hypersecretion, which appears to be connected with salt and water loss.