The administration of 30 mg of prednisolone on an alternate-day schedule produced an increase in sodium and potassium excretion, followed by a compensatory decline on the succeeding nontreatment day. Water and electrolyte excretion in patients receiving a daily steroid treatment was intermediate between that on the treatment and nontreatment days in the patients on an alternate-day schedule. Fractional sodium and potassium excretion was significantly lower on the nontreatment days as compared to the treatment days. Body weight loss, elevated serum albumin, slightly reduced serum potassium and significantly decreased cortisol concentrations were found in the morning on the nontreatment days, while serum sodium and plasma aldosterone concentrations, and the creatinine clearance rate did not change significantly. Replacement of steroid-induced body fluid loss lessened a decline in water and electrolyte excretion on the nontreatment days. Reduced water and electrolyte excretion on the nontreatment days might have been associated with decreased extracellular fluid volume, suppressed cortisol secretion, or both.