SUMMARY1. Thallium (Ti) inhibits the ouabain-sensitive K influx in human red cells in high-Na medium. At 1 mm external K concentration [K.], the ouabain-sensitive K influx decreases steadily with increasing Ti concentration, up to 0-9 mm outside; at 0-17 mM-K., however, Ti stimulates the ouabain-sensitive K influx below 0.1 mM-Ti0 and inhibits it at higher concentrations.2. In a K-free medium in which all except 5 mM-Na is replaced by choline, and into which red cells show zero control ouabain-sensitive Na efflux, Ti is able to support ouabain-sensitive Na efflux up to 2-1 m-mole/l. cells. hr following a sigmoid activation curve which is half-maximal between 0 03 and 0.05 mM-TiO and that follows two-site kinetics up to 0 I mM-Tlo. Beyond 0 15 mm-TiO, the Ti-activated ouabainsensitive Na efflux attained is inhibited slightly.3. When the ouabain-sensitive Na efflux is measured at 5 mM-Na0 and 5 mM-K0, increasing concentrations of Ti have little effect on it, 0.9 mM-TiO inhibiting by some 14 %; in similar conditions, the ouabainsensitive K influx is inhibited by about 40 %.4. The dependence of ouabain-sensitive K influx on external K concentration at 5 mm-Nao, which follows a slightly sigmoid curve in the absence of Ti, changes to hyperbolic at 0-06 mM-Tlo at the same time that ouabain-sensitive K influx is inhibited. The fitted Vmax values for ouabainsensitive K influx are the same in the presence and in the absence of 0x06 mM-Tlo.5. In high-Na cells, loaded by nystatin treatment, the ouabainsensitive K influx measured at 0-2 mM-Nao follows a hyperbolic curve between 0-05 and 0 4 mM-K0, and is inhibited by Ti in a strictly competitive fashion.6. The effects of Ti on ouabain-sensitive Na efflux and ouabainsensitive K influx are interpreted in terms of a high-affinity substitution for K at the external K sites of the Na pump and suggest that in human red cells Ti can be actively transported inwards in exchange for internal Na. J. D. CAVIERES AND J. C. ELLORY 7. Thallium can inhibit about 25 % of the ouabain-insensitive Na efflux into 5 mM-Na0 and part of this inhibition occurs with a high TI-affinity; the ouabain-insensitive K influx is inhibited by Ti both in high-Na and in 5 mm-Na medium, but with a different concentration dependence than the ouabain-insensitive Na effilux.