The exchangeability of toad bladder epithelial cell potassium has been investigated. An insignificant amount of cellular potassium exchanged with mucosal medium 42K. From the rate of uptake of 42K into the cells from the serosal medium at least two cellular potassium pools were identified. The more rapidly exchanging pool contained about one-quarter to one-third of the cellular potassium and exchanged with a half-time of about 30 min. It was from this pool that potassium was lost from cells exposed to ouabain or to a potassium-free medium. In addition, when 3.5 mM rubidium replaced 3.5 mM potassium in sodium Ringer's the epithelial cells lost in 60 min about one-quarter of their cellular potassium in exchange for rubidium. Inhibition of transepithelial sodium transport by amiloride, 10(-5) mM, seemed to depress the rate of potassium uptake into the more rapidly exchanging pool without affecting total cellular potassium content. However, stimulation of transepithelial sodium transport by vasopressin appeared not to affect the rate of potassium uptake. The rate of potassium uptake into this pool seemed much less than that required for a tight 1:1 coupling between transepithelial sodium transport and potassium uptake. The remaining cellular potassium exchanged at a much slower rate and even after 19 hours of incubation only 67% of cellular potassium was labelled. If this slower exchanging potassium represents a single pool, 99% of cellular potassium would be labelled only after incubation with 42K for 56 hours.