In the management of patients with congestive heart failure (CHF), it is often desirable to have precise knowledge of overall renal function, including the effective renal plasma flow (ERPF). It has long been recognized that ERPF is diminished in CHF. Since glomerular filtration rate is often decreased to a much lesser extent, other noninvasive procedures such as the measurement of creatinine clearances may not be entirely suitable. ERPF determination by the single plasma sampling (SPS) method affords a rapid, simple, noninvasive, and economical technique that is quite accurate and reproductible. A SPS method has been well-tested in patients following renal transplantation plus a wide variety of nephrological disorders. We have been concerned whether the SPS method would be valid in volume expanded patients. In 28 determinations of ERPF in patients with CHF, and in five patients who did not have CHF, we have found the SPS estimation of ERPF to yield results that are not clinically significantly different from those obtained by the detailed compartmental analysis method. The volumes of 131I-orthoiodohippurate (OIH) distribution were found to be somewhat higher in CHF than in controls, but fractional rate constants were proportionately lower so that intercompartmental flow rates and OIH concentrations were not different from controls. Therefore, the SPS estimation of ERPF is valid in patients with CHF and may be useful in monitoring the renal effects of various hemodynamic and pharmacological interventions. © 1981 Springer-Verlag.