The uptake and efflux of 22Na was studied in isolated rat uterine horns (both fresh and Na-rich) at 5, 15, 25, and 37 °C. Reduction of temperature from 37 °C to 25 or to 15 °C reduced 22Na uptake into, and efflux from, both the extracellular space and cells to the degree expected of a diffusion-controlled process (Q10 < 2). Reduction of the temperature to 5 °C during uptake into Na-rich horns revealed that a substantial fraction of cellular sodium became less exchangeable. At 5 °C, 22Na efflux was also markedly reduced, more than from ouabain or ATP depletion. Analysis of this change by curve-peeling and by reducing the temperature at various stages of efflux suggested that the main cause was a shift of 22Na from the larger, faster cellular fraction (No. 2) to the slower cellular fraction (No. 3). Bound 22Na was also markedly increased. The rate coefficients from curve-peeling for both cellular fractions were decreased. Radioactivity still in fraction 2 at 5 °C emerged at a rate of about half that at 15 °C. However, an overall coefficient for efflux of 22Na which would have emerged in fraction 2 at 15 or 25 °C showed that the Q10 for 22Na efflux between 5 and 15 °C was about 15. Tissues did not swell when they gained sodium at 5 °C. The effects of ouabain to increase 22Na influx and 42K efflux were eliminated at 5 °C. The effects of ATP depletion by iodoacetate and dinitrophenol to decrease 22Na efflux and to increase 22Na uptake, K loss, and swelling were reduced at 5 °C. Prior ATP depletion altered but did not prevent the marked reduction of efflux by cooling to 5 °C. Efflux of lithium, but not of potassium, was markedly slowed at 5 °C. K-free solutions still increased 22Na uptake at 5 °C. A model involving pinocytotic vesicles to explain these and earlier results was postulated.