Infusion of para-aminohippurate (PAH) during renal clearance experiments has been shown to increase urinary sodium excretion (UNAV). In addition, it has recently been suggested that accumulation of PAH and/or related compounds may be responsible for the increased UNAV per nephron in chronic renal failure. Therefore, studies were designed to determine the mechanism for the natriuretic effect of PAH. PAH administration at (0.19 mM per minute) into the dog renal artery led to an average increase in UNAV of 56+/-11 muEq per minute. Mannitol given at this rate (0.19 mM per minute) led to an increase in UNAV of 26+/-10 muEq per minute, which was less than the increase in UNAV with PAH. NA2SO4 given at this (0.19 mEq per minute) or a higher rate (0.60 mEq. per minute) was associated with an increase in UNAV of 53+/-18 and 228+/-38 muEq per minute, respectively. In the PAH and SO4 studies the increase in UPAHV or USO4V was not different from the increase in UNAV. These results suggest that the natriuretic effect of PAH is mainly due to its effect as a nonreabsorbable anion and offer no support for an osmotic effect or a direct effect on active sodium transport.