The action of theophylline on both sodium efflux and influx was measured using freshly isolated frog sartorius muscles. In normal Ringer's fluid, 2 mM theophylline increased sodium efflux by 35% whereas it decreased sodium influx by about 10%. The percent increase in sodium efflux produced by 2 mM theophylline was not significantly altered in sodium-free, lithium-containing solutions. Strophanthidin prevented the stimulation of sodium efflux by 2 mM theophylline in both normal, sodium-containing Ringer's fluid and sodium-free, lithium-containing solutions. Hence, the major effect of theophylline seems to be stimulation of active sodium transport and the enhanced rate of sodium exit induced by theophylline does not seem to require the presence of external sodium. An interesting and unexplained findings is that 2 mM theophylline, which does not produce a maximal stimulation of sodium efflux, prevents the increased sodium efflux induced by saturating doses of epinephrine.