The effects of p-aminohippurate (PAH) on electrolyte clearances were measured in 8 human volunteers. At plasma PAH levels used to measure renal plasm flow, the only significant increase was in sodium clearance, while with PAH levels used to measure maximum tubular secretion, the clearances of sodium, potassium and phosphorus were all significantly increased. The antriuresis combined with a depression of free water clearance and the absence of a chloruresis led to the conclusion that PAH- changed the anion composition of the filtrate delivered to the ascending limb, thus interfering with coupled Na+ reabsorption. This finding must be taken into account when electrolyte excretion is being measured during PAH infusion. A similar mechanism may operate in patients with chronic uremia whose endogenous hippurate level is increased.