It is known that atrial extracts (AE) and synthetic atrial natriuretic factor (ANF) can increase glomerular filtration rate (GFR) and electrolyte and water excretion both in vivo and in vitro. It is not clear, however, if ANF-induced increases in filtered load (increased GFR) are required to produce natriuresis and diuresis. We perfused isolated rat kidneys with AE or synthetic ANF at constant pressure in a single-pass system. Extracts of atrial tissue (1 mg/ml) and high concentrations of ANF (31 and 61 ng/ml) significantly increased both GFR and electrolyte and water excretion. During continued infusion of ANF, GFR stabilized at increased levels, but sodium and water excretion continued to increase. After the termination of infusions, GFR and potassium excretion returned to control levels, but sodium and water excretion remained significantly elevated. Infusion of a low concentration of ANF (3 ng/ml) significantly increased sodium and water excretion without changing either GFR or potassium excretion. We conclude that increases in GFR are not a prerequisite for natriuresis and diuresis in response to ANF, but that increases in GFR can potentiate the response. Furthermore, our data suggest that ANF increases potassium excretion only if it increases GFR.