The effects of Pb2+ added in vitro to tissue slices, isolated tubules and isolated mitochondria of rat kidney cortex have been studied. Slices were depleted of K+ and loaded with Na+, Cl- and water by pre-incubation at 1C, and reversal of these changes was then induced by incubation under metabolically favorable conditions. The net reaccumulation of K+ was reduced by a maximum of 30% when Pb2+ was present in the medium, the maximal effect being caused by 200 micromoles Pb2+. Lead also caused a reduction of Na+ extrusion which was approximately equimolar with its effect on K+, but it did not affect the extrusion of Cl- and water. The initial rates of the net, active movements of K+ and Na+ were not altered by Pb2+, divergence from control values only being noted after 15-30 min incubation.