The principle aim of the present study was to provide evidence for the existence of both a luminal and a basolateral mechanism involved in the renal tubular uptake of inorganic mercury. To accomplish this aim, we examined individually and collectively the effects of a "stop-flow" technique designed to reduce glomerular filtration to negligible levels and pretreatment with the organic anion p-aminohippurate (PAH) on the renal uptake and disposition of administered inorganic mercury. More specifically, we compared the disposition of inorganic mercury in groups of surgical control rats, rats that underwent a unilateral ureteral ligation, and rats that underwent a bilateral ureteral ligation that were pretreated with either normal saline or a 7.5 mmol/kg intravenous dose of PAH 5 min prior to receiving a nontoxic 0.5-mumol/kg intravenous dose of mercuric chloride. The disposition of mercury was evaluated at both 1 h and 24 h after the dose of inorganic mercury had been administered. In brief, the "stop-flow" conditions induced by either unilateral or bilateral ureteral ligation caused a significant reduction in the uptake and content of mercury in the kidneys (whose ureter was ligated) both at 1 h and 24 h after the intravenous injection of the nontoxic dose of mercuric chloride. This decreased renal uptake of mercury was due specifically to decreased uptake of mercury in the renal cortex and outer stripe of the outer medulla. Assuming that glomerular filtration was reduced to negligible levels, the amount of mercury not taken up during ureteral ligation represents the portion of mercury that is presumably taken up by a luminal mechanism. Pretreatment with PAH also caused a significant reduction in the renal uptake of mercury, specifically in the cortex and outer stripe of the outer medulla. The effects were most prominent 1 h after the injection of inorganic mercury. When either unilateral or bilateral ureteral ligation was combined with PAH pretreatment, an additive inhibitory effect occurred with respect to the renal uptake of mercury. In fact, the renal uptake of mercury was reduced by approximately 85% at 1 h after the injection of mercuric chloride. Since the luminal uptake of mercury was blocked by ureteral ligation, the effect of PAH on the renal uptake of mercury must have occurred at the basolateral membrane. Thus, the findings from the present study indicate that there are two distinct mechanisms involved in the uptake of mercury, with one mechanism located on the luminal membrane and another located on the basolateral membrane (presumably on proximal tubular epithelial cells).