Technetium-99m-EC has recently been introduced as an alternative renal tubular agent to I-131-ortho iodohippurate (OIH). It has been shown that Tc-99m-EC clearance shows strong correlation with OIH clearance and it is possible to estimate effective renal plasma flow. In routine clinical studies, it is practical to use one or two plasma sample methods instead of multiple plasma samples for clearance determination. An attempt was made to determine Tc-99m-EC clearance with one sample method. Methods: Data from 72 subjects were collected. To increase the range of renal function, two anuric hemodialysis patients were also included. Clearances were determined by the open two-compartment model. Results: The clearance range was 12 ml/min to 660 ml/min with a mean of 275 +/- 117 ml/min. Analysis of correlation was made by Tauxe's method. The least standard error of estimation (s.e.e. = 32.71 ml/min) and the best correlation (r = 0.97) between the theoretical volume distribution and the clearance estimations were obtained from the 54-min plasma sample. Conclusion: This study suggests that EC clearance could be determined by a simplified single-sample method with an acceptable s.e.e.