An experiment was designed to compare the effects of chlorothiazide, furosemide, ethacrynic acid and MK870 on cortico-medullary gradients of sodium and urea in the rat kidney. The sodium concentration gradient did not fall significantly after treatment with chlorothiazide and there was no increase in the water content of the papillary tip. Furosemide, ethacrynic acid and MK870 reduced the sodium concentration but not the sodium content of the outer medulla and papillary tip. This effect was shown to be due to a marked increase in the water content of these tissues. The results are not consistent with the theory that furosemide and ethacrynic acid block sodium reabsorption in the ascending limb of the loop of Henle of the rat. Furosemide and ethacrynic acid had similar effects on the gradients, yet, of the two, only furosemide produced a significant natriuresis in the rat. All the diuretics produced a marked depletion of medullary urea.