The effect of intravenous administration of the loop diuretics bumetanide, furosemide and ethacrynic acid on lithium (Li) clearance (CLi) and diluting segment reabsorption was studied in seven healthy water-loaded men. According to the increments in minimal urine osmolality (Uosm), ethacrynic acid (which increased Uosm from 59 +/- 4 to 233 +/- 3 mOsmol/kg) had the strongest inhibiting effect on diluting segment reabsorption, whereas that of furosemide and especially bumetanide was significantly less pronounced (rise in Uosm from 56 +/- 3 to 222 +/- 4 and 56 +/- 4 to 192 +/- 2 mOsmol/kg, respectively). In contrast, ethacrynic acid induced a significantly smaller rise in CLi (approximately 14% of the filtered load of Li) than furosemide and bumetanide, which increased Li excretion by approximately 23% and approximately 24% of its filtered load. The observation that the loop diuretic with the most pronounced inhibiting effect in the diluting segment had the smallest effect on CLi makes is unlikely that the increase in CLi induced by loop diuretics is predominantly effected in Henle's loop.