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The renal site of action of organomercurials has variously been placed within the proximal or distal tubule on the basis of numerous observations in dog and man (1-9). Experiments in maximally hydrated man recently reported from this laboratory showed that free water clearance remained relatively fixed throughout the major portion of the diuresis induced by the organomercurial, meralluride (10). In addition, free water clearance could generally be augmented by superimposing a nonspecific solute diuretic ' during the mercurial diuresis. A hypothesis was suggested that placed a major inhibitory action of organomercurials at a late distal segment, beyond the water-clearing site where, it was assumed, a process of isosmotic salt and water reabsorption takes place. Previous data concerning the effect of mercurial diuresis on the concentrating operation in hydropenic man have led to varied conclusions. Some have argued that a mercurial diuresis limits the renal concentrating capacity (11). Others have found that a mercurial diuresis superimposed upon or developing simultaneously with a nonspecific solute diuresis does not limit the capacity of the collecting duct to extract solute-free water (12, 13). Medullary hypertonicity is established primarily by the deposition within the interstitium of salt absorbed from the ascending limb of the loop of Henle. Under conditions of maximal hydropenia, the variable hypotonicity produced in the ascending limb is dissipated by the outward diffusion of water through a permeable tubular mem-

EFFECT OF ORGANOMERCURIALS ON THE RENAL CONCENTRATING OPERATION IN HYDROPENIC MAN: COMMENTS ON SITE OF ACTION*