1. The entry of Li into the vascular smooth muscle cells of the rat tail artery follows first-order kinetics with a rate constant of approximately 1.3 hr(-1) at 10 mM-[Li](o). The rate constant decreases gradually to ca. 0.5 hr(-1) when the [Li](o)/[Na](o) ratio is increased.2. Replacement of Na with Li over the range of [Li](o) from 1 to 115 mM, accomplished at constant ionic strength and osmolarity of the bathing solution, produces changes in cell Na and K without apparent change in cell water. At equilibrium, cell Li increases in linear proportion to [Li](o), at a ratio of 2:1 throughout the range. The increase in cell Li is associated with inverse falls in both cell K and Na such that the ratio of cell K to cell Na remains constant at ca. 10:1 throughout.3. The changes in the ionic contents, induced by equilibration of the tissue with a Na-free, Li-substituted solution, are reversible.4. Replacement of Na with sucrose over the range of 40-115 mM results, at equilibrium, in a linear fall in cell Na without conspicuous change in cell K. A constant portion of the cell Na, ca. 10 m-mole/kg dry wt., does not participate in this exchange.5. At equilibrium, reductions in [Na](o) are reflected in corresponding reductions in apparent [Na](i) such that the [Na](o)/[Na](i) ratio remains constant.