In animals on a normal NaCl intake despite the repeated administration of a diuretic Cl and Na excretion return to baseline values after initial Cl and Na loss. In order to delineate whether this apparent resistance is consequent primarily on a decreased effect of the diuretic, or compensatory Cl and Na reabsorption when the diuretic is not acting, rats were injected with frusemide (1.5 mg twice a day intraperitoneally for 4 days) while on diets differing in Cl and Na content. On a normal NaCl diet Cl and Na excretion increased on day 1 and subsequently returned to baseline. On a low NaCl diet Cl and Na excretion remained above baseline on all 4 days, thereby demonstrating that frusemide continues to promote daily Cl and Na loss. On a low Cl-normal Na intake Na excretion returned to baseline after day 1, while Cl excretion remained above baseline on all 4 days. The increase in K and net acid excretion was highest in these studies. On a low Na-normal Cl intake Cl excretion returned to baseline after day 2, while Na excretion exceeded baseline on all 4 days. Daily K excretion increased least and net acid excretion decreased in these studies. Hourly data on all four diets indicate that frusemide always has an acute effect to promote both Cl and Na excretion. In the recovery period Cl or Na reabsorption is enhanced when the respective ion is available. The apparent resistance to daily frusemide administration on a normal NaCl intake is primarily consequent on enhanced reabsorption balancing the chloriuretic and natriuretic effects. Daily changes in K and net acid excretion are also determined, in part, by these opposing effects.