We examined the effect of lithium on rat renal handling of p-aminohippurate (PAH) and accumulation of organic ions by rat kidney cortical slices. When infused intravenously with lithium at the rate of 0.13 mmoles/kg/min, decreased renal clearance of PAH as well as no significant changes in glomerular filtration rate and plasma PAH level was observed at the first clearance period during lithium infusion. As we expected, tubular secretion of PAH also was decreased significantly by the infusion of lithium. Therefore, it is suggested that the decrease in the clearance of PAH was due to the decrease in the tubular secretion of PAH. After four days of injections with lithium (4 mmoles/kg, i.p., once a day), a significant decrease in PAH accumulation in the slices was detected. No inhibition of tetraethylammonium accumulation was observed. Lithium pretreatment did not alter water content and extracellular space of the slices. The results suggest that lithium selectively inhibits the organic anion transport system in kidney with the in vivo treatment and follows our previous work in which we showed the in vitro effect of lithium on organic anion accumulation in the slices.