In the present study, pretreatment with p-aminohippurate (PAH) and induction of stop-flow conditions (by ureteral ligation) were used as tools to determine whether the enhanced accumulation of injected inorganic mercury that occurs in the renal outer stripe of the outer medulla in rats following uninephrectomy and compensatory renal growth is due to a luminal and/or basolateral mechanism. The effects of these pretreatments on the disposition of mercury in the liver and blood were also evaluated as a secondary aim. Pretreatment of both uninephrectomized (NPX) and control rats with a 7.5 mmol/kg dose of PAH 5 min prior to the injection of a nontoxic 0.5 mumol/kg i.v. dose of mercuric chloride caused a significant decrease in the renal accumulation of mercury in both control and NPX rats during the initial 3 h after the injection of inorganic mercury. However, the concentration of mercury in the renal outer stripe of the outer medulla was significantly greater in the NPX rats than in the corresponding control rats. Induction of stop-flow conditions (by i.v. bolus injection of 2.0 mmol/kg mannitol followed 5 min later by ureteral ligation) approximately 75 min prior to the injection of inorganic mercury also resulted in decreased renal accumulation of mercury in both NPX and control rats. In contrast to the effects of PAH, induction of stop-flow conditions resulted in the concentration of mercury in the renal outer stripe of the outer medulla in the NPX rats being statistically equivalent to that in the corresponding control rats 3 h after the injection of mercury. Assuming that glomerular filtration rate was reduced to negligible levels in these animals, the fraction of mercury that was not taken up and accumulated in the outer stripe of both groups of rats represents the fraction of mercury that is taken up by a luminal mechanism. Thus, on the basis of the findings in this study, it appears that the increased accumulation of mercury that occurs in the renal outer stripe of the outer medulla in NPX rats is linked to a luminal mechanism, presumably localized in the epithelial cells lining the proximal tubule. Finally, when pretreatment with PAH and induction of stop-flow conditions were combined, there was additivity with respect to decreased renal accumulation of mercury. This additivity provides further support for the current hypothesis that there are both luminal and basolateral mechanisms involved in the renal uptake of inorganic mercury.