Chromium-51 ethylene diamine tetra-acetic acid (Cr-51-EDTA) total plasma clearance was evaluated using a multi-sample method (i.c. 12 blood samples) as the reference compared with several simplified methods which necessitated only one or few blood samples. The following 5 methods were evaluated: terminal slope-intercept method with 3 blood samples, simplified method of Brochner-Mortensen and 3 single-sample methods (Constable, Christensen and Groth, Tauxc). Linear regression analysis was performed. Standard error of estimate, bias and imprecision of different methods were evaluated. For Cr-51-EDTA total plasma clearance greater than 30 ml.min-1, the results which most approximated the reference source were obtained by the Christensen and Groth method at a sampling time of 300 min (inaccuracy of 4.9%). For clearances between 10 and 30 ml.min-1, single-sample methods failed to give reliable results. Terminal slope-intercept and Brochner-Mortensen methods were better, with inaccuracies of 17.7% and 16.9%, respectively. Although sampling times at 180, 240 and 300 min are time-consuming for patients, Cr-51-EDTA total plasma clearance can be accurately calculated for values greater than 10 ml-min-1 using the Brochner-Mortensen method. In patients with clearance greater than 30 ml.min-1, single-sample techniques provide a good alternative to the multi-sample method; the choice of the method to be used depends on the degree of accuracy required.