The natriuretic and diuretic effectiveness of once-daily and twice-daily furosemide administration schedules was compared in a two-way crossover study using six normal subjects. Urine was collected for 24hours before and after administration of the first dose of furosemide. Patients received one 40-mg dose or two 20-mg doses of the drug administered six hours apart. Sodium and potassium urine concentrations were measured through flame emission photometry using lithium as an internal standard. Chloride urine concentrations were determined using colorimetric measurement with mercuric thiocyanate. Results were statistically evaluated by a one-way analysis of variance. Results showed no statistically significant differences (p greater than 0.7) between the two regimens in the cumulative 24-hour excretion of sodium, potassium, chloride or water. The average 24-hour sodium excretion following a single 40-mg furosemide dose was 268.9 mEq, while that following administration of the two 20-mg doses was 294.2 mEq. Differences during various intervals within the 24-hour collection period were consistent with the relative sizes of doses administered. It would appear that single daily dose administration regimens would be a logical beginning for furosemide therapy, particularly when lower doses are being considered.