The renal clearance of sodium iothalamate I125 after a single intravenous dose of 10 to 25 µCi was calculated from the plasma disappearance curve. The endogenous creatinine clearance was compared with these results. Thirty-eight studies in 35 pediatric patients with all levels of renal function were performed. Eight studies were excluded because of grossly incomplete urine collection, and 5 studies were not analyzed further because of very low glomerular filtration rate. The correlation between both methods in the 21 studies was good (Ccreat = 0.91 x Csi + 4.9, r = 0.91). It was significantly better in the nine patients with a serum creatinine of 0.7 mg/100 ml or more (Ccreat = 1.01 x Csi — 1.2, r = 0.97) than in the 16 patients with a serum creatinine of 0.6 mg/100 ml or less (Ccreat = 0.82 x Csi + 11.5, r = 0.84). In the latter group, the accuracy of the serum creatinine determination was often poor, and even variations of ± 0.1 mg/100 ml could lead to a gross error in the calculation of the clearance. In four patients, the clearance was obtained by external counting and agreed well with the clearance calculated from the plasma samples. The single injection clearance is especially indicated in children (1) when no adequate urine collection is obtainable, (2) at low serum creatinine concentrations, and (3) in outpatients.