SUMMARY1. Tissues were allowed to equilibrate in a Tris-buffered Krebs solution and were then exposed to similar solutions containing up to 5 mM-La. La 3. Subtraction of the ions in the measured [14C]sucrose space from the total tissue ion contents led to estimates of the 'cellular' ion contents. The effects of 1 hr exposure to 5 mM-La on these were a loss of 12*9 + 2*4 m-equiv/kg of cation and a gain of 10 0 + 2-6 m-equiv/kg of Cl.4. Similar changes in ion content were produced by La on 'Na-loaded' and 'K-loaded' tissues, these being tissues which by exposure to K-free or Na-free (high K) solutions had replaced all their K with Na or vice versa.5. The uptakes of 24Na and 36CI by Na-loaded tissues were both describable as the sum of two exponential processes: a fast component (t* I min), which was presumed to be extracellular and a slower, presumed transmembrane, component. La reduced the rapid component of uptake of 24Na by an amount greater than that predicted by the reduction in the e.c.s., the extra amount lost being some 10-15 m-equiv/kg. La also reduced the amount of rapidly exchanging 3601, but this reduction was entirely accounted for by the change in the e.c.s. La reduced the rate constant of the slow component of 24Na uptake.A. F. BRADING AND J. H. WIDDICOMBE 6. La reduced the rapidly exchanging component of 42K uptake by normal tissues by an amount equivalent to about 0.5 m-mole/kg fresh wt. of K in excess of the change in the extracellular space.7. La had little effect on the effluxes of 36CI and 42K from normal tissues. However, it reduced the size of the fastest component of exchange of 42K efflux from K-loaded tissues by an amount equal to some 10-15 m-equiv/kg in excess of the reduction in the e.c.s. A similar reduction in the rapidly exchanging component of 24Na efflux from normal tissues was also seen. La slowed the efflux of 24Na from Na-loaded tissues at times when the tracer lost could safely be regarded as intracellular.8. The taenia coli when exposed to K-free solutions gains Na and loses K. In the presence of La the gain in Na was completely blocked. K was still lost, however, being accompanied by Cland increased shrinkage. La also prevented the uptake of Na from high Na media by ion-depleted tissues (produced by exposure to sucrose media), while having little effect on the uptake of K from high K media by such tissues.9. The cation displaced by La in excess of that lost due to the reduction of the e.c.s. was shown by tracer studies to be rapidly exchanging. It is concluded that this cation, amounting to some 15-20 m-equiv/kg, is bound to fixed extracellular negative sites.