Glomerular filtration rate (GFR) can be calculated from the plasma clearance of any of several radiopharmaceuticals that are excreted by glomerular filtration. Simplified methods have been proposed that require only one or two plasma samples in lieu of a more complete clearance curve. We examined the error introduced by this simplification. Forty patients were studied using a dual-isotope technique employing [99mTc]DTPA and [169Yb]DTPA, obtaining eight plasma samples for each clearance curve at intervals from 10 to 240 min after injection. Data were fit to several empirical or semiempirical formulae and also to a two-compartment computer model that permitted GFR estimation from only one or two data points. The computer model gave good fit, but so did several simpler methods. The error that results from replacing the complete clearance curve by a single 3-hr sample was about 8 ml/min (residual s.d.). By using two samples (at 1 and 3 hr), the error could be reduced to 4 ml/min. Recommended one- and two-sample methods are presented.