OBJECTIVES: To measure glomerular filtration rate using iohexol plasma clearance (mGFR(iohexol)) in critically ill patients using the high doses of iohexol administered at CT and to evaluate its agreements with urinary creatinine clearance (uCl(cr)) and estimated glomerular filtration rates (eGFRs), calculated from plasma concentrations of creatinine (eGFR(cr)) and cystatin C (eGFR(cys)). DESIGN: Prospective observational cohort study. SETTING: ICUs across Southeast Sweden. PATIENTS: Critically ill adult patients. INTERVENTIONS AND MEASUREMENTS: Twenty-six ICU patients were given high doses of iohexol (range, 27-140 mL) for contrast-enhanced CT, whereafter blood samples were taken in the elimination phase for determination of mGFR(iohexol). Plasma iohexol concentrations were determined by high-performance liquid chromatography and mGFR(iohexol) was calculated. Standard dose (5 mL) of iohexol was administered the following days to compare low-dose clearance results with the high-dose clearance results. Six-hour uCl(cr) was performed four times a day and averaged. MAIN RESULTS: Mean +/- sd mGFR(iohexol) after CT was 77.4 +/- 38.1 mL/min (n = 26), and uCl(cr) was 97.3 +/- 58.2 mL/min (n = 25) in the critically ill patients. There was a strong positive correlation between mGFR(iohexol) determined with high and low doses of iohexol in patients with normal or high mGFR(iohexol) (coefficient of determination [R-2] = 0.88; p < 0.001) and between mGFR(iohexol) and uCl(cr) (R-2 = 0.87; p < 0.001). eGFR(cr) overestimated mGFR(iohexol) and eGFR(cys) underestimated mGFR(iohexol). CONCLUSIONS: mGFR(iohexol) after contrast-enhanced CT compares well with mGFR(iohexol) after standard low-dose iohexol respectively uCl(cr). Over- and underestimation of mGFR(iohexol) by eGFR(cr) and eGFR(cys) is probably explained by increased tubular secretion of creatinine and increased production of cystatin C in intensive care patients.