Fifty-three determinations of effective renal plasma flow (ERPF) were made on 21 patients with a wide range of renal function. Serial plasma samples for 6 hours after the injection of 125I-orthoiodohippurate were used to plot the plasma disappearance curve, and a standard ERPF was calculated using biexponential analysis of the curve. ERPF values calculated by 3 published approximation methods using limited plasma samples were compared to the standard values. All approximation methods overestimated the ERPF, the mean percentage error lying between + 18.3% +/- 20.4% and + 70.0% +/- 51.3%. With 2 of the 3 approximation methods the overestimation was particularly prominent in patients with moderate to severe renal insufficiency (ERPF less than 300 ml/min). For research purposes the more accurate and reliable biexponential method of analysis of ERPF is recommended.