We tested the hypothesis that the hyponatremia commonly observed in patients with acute hepatic porphyria is mediated by the presence of aminolaevulinic acid (ALA) and (or) porphobilinogen (PBG) at the level of the renal tubule to alter water handling, or at the level of the nervous system to release antidiuretic hormone (ADH). When these substances were infused intravenously into hydropenic dogs, there was no effect on systemic hemodynamics or renal function. Neither ALA or PBG, when infused directly into the renal circulation of water-loaded dogs, could effect a decrease in urinary flow, osmolar clearance, or renal perfusion. Similar results were obtained when these substances were infused directly into the renal circulation of hydropenic dogs. When ALA was administered directly into the carotid artery of nine water-loaded dogs and eight hydropenic dogs, there was again no effect on systemic hemodynamics or renal function. These data suggest that ALA (and PBG) have no effect on the renal excretion of sodium or water, and ALA does not cause the release of ADH. The hyponatremia of porphyria may be related to factors other than the elevated plasma levels of ALA and PBG.