The loop diuretics are drugs that increase the excretion of water and electrolytes in the urine by their action on the cells in the loop of Henle. Clinical reports of ototoxicity of these agents are reviewed, and the results of a number of studies in experimental animals are discussed. These drugs can cause either a temporary, or in some cases, a permanent loss of hearing in patients. Animal experiments show that these drugs act on the stria vascularis, producing edema of these tissues and a temporary loss of function, resulting in a decrease of the endocochlear potential. This can result in secondary effects on sound-evoked measures of hearing. As new information unfolds about protective agents, it may be possible to preserve hearing and maintain the desired therapeutic effect.