The accumulation and handling of mercury in the blood, kidneys, and liver were evaluated and compared in rats 5 min, 1 h, and 24 h after the intravenous administration of either a 0.25 mumol/kg dose of inorganic mercury or a 0.25 mumol/kg dose of inorganic mercury plus a 0.5 mumol/kg dose of glutathione (GSH) to determine the possible role of extracellular GSH and complexes of GSH and inorganic mercury in the renal uptake and transport of inorganic mercury. Significantly more of the injected dose of inorganic mercury was present in the blood of the rats injected with inorganic mercury alone than in the blood of the rats injected simultaneously with both inorganic mercury and GSH at all times evaluated after injection. Of the mercury remaining in the blood, however, significantly more mercury was in plasma fraction of blood in the rats injected with both inorganic mercury and GSH than in the plasma fraction of blood in the rats injected with inorganic mercury alone. The blood and plasma findings indicate that much of the mercury injected with GSH was in some complex that allowed the mercury to be cleared from the blood more readily and prevented the mercury from entering readily into red blood cells. The renal concentration of mercury was significantly greater in the rats injected with both inorganic mercury and GSH than in the rats injected with inorganic mercury alone at 5 min and 1 h, but not 24 h, after injection. This increased renal accumulation of mercury during the initial hours after injection was due mainly to enhanced uptake and/or retention of mercury in the renal cortex. Urinary excretion of mercury, over 24 h, was also slightly, but significantly, greater in the rats injected with both inorganic mercury and GSH simultaneously. These data indicate that coadministration of a nontoxic dose of inorganic mercury with a twofold higher amount (in moles) of GSH increases significantly the clearance of mercury from the blood and increases the renal cortical accumulation of inorganic mercury during the initial 1 h after injection. Moreover, the data in this study are consistent with the hypothesis that extracellular GSH is an important ligand to which mercuric ions bind, and that complexes of inorganic mercury and GSH in the blood and/or ultrafiltrate probably play a role in the renal uptake of some of the mercury in blood after exposure to mercuric compounds.