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The effect of contrast media on renal extraction of para-aminohippurate (PAH) was studied experimentally in dogs. Fifty per cent sodium diatrizoate, 60% meglumine diatrizoate and 60% meglumine iothalamate at a dose of 0.3 ml/kg body wt., delivered into the renal artery, produce a consistent fall in EPAH measured at 30 sec after injection with return to control levels several minutes thereafter. Similar volumes of physiologic saline resulted in no consistent change in EPAH. Mannitol, 26.5% and sodium chloride (hypertonic), 4.5% caused a diminished EPAH, comparable to the contrast agents, as did 12% meglumine diatrizoate (isotonic). The data indicate that the bolus effect, pH, and sodium content are not important in the genesis of the fall in EPAH. For the contrast media in current use, it appears that the N-methylglucamine cation and/or organic iodinated molecule is capable of inducing a decrease in EPAH, exclusive of the effect of hypertonicity, but it is likely that the latter plays a significant role. Further experiments are outlined to resolve this question.