Transpulmonary double-indicator dilution is a useful monitoring technique for measurement of intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). In this study, we compared a simpler approach using single arterial thermodilution derived measurements of ITBV and EVLW with the double-indicator dilution technique. Prospective observational clinical study. Surgical intensive care units of two university hospitals. Global end-diastolic volume (GEDV) derived from single thermodilution was used for calculation of ITBV. Structural regression analysis of the first two thermo-dye dilution measurements in a derivation population of 57 critically ill patients (38 male, 19 female, 18-79 years, 56 +/- 15 years) revealed ITBV = (1.25 x GEDV)-28.4 (ml). This equation was then applied to all first measurements in a validation population of 209 critically ill patients (139 male, 70 female, 10-88 years, mean 53 +/- 19 years), and single-thermodilution ITBV (ITBV(ST)) and EVLW (EVLW(ST)) was calculated and compared to thermo-dye dilution derived values (ITBV(TD), EVLW(TD)). For inter-individual comparison, absolute values for ITBV and EVLW were normalised as indexed by body surface area (ITBVI) and body weight (EVLWI), respectively. Linear regression analysis yielded a correlation of ITBVI(ST) = (1.05 x ITBVI(TD))-58.0 (ml/m2), r = 0.97, P < 0.0001. Bias between ITBVI(TD) and ITBVI(ST) was 7.6 (ml/m2) with a standard deviation of 57.4 (ml/m2). Single-thermodilution EVLWI (EVLWI(ST)) was calculated using ITBVI(ST) and revealed the correlation EVLWI(ST) = (0.83 x EVLWI(TD)) + 1.6 (ml/kg), r = 0.96, P < 0.0001. Bias between EVLWI(TD) and EVLWI(ST) was -0.2 (ml/kg) with a standard deviation of 1.4 (ml/kg). In detail, EVLWI(ST) systematically overestimated EVLWI(TD) at low-normal values for EVLWI and underestimated EVLWI at higher values (above 12 ml/kg). Determinations of ITBV and EVLW by single thermodilution agreed closely with the corresponding values from the double-indicator technique. Since transpulmonary single thermodilution is simple to apply, less invasive and cheaper, all these features make it a promising technique for the bedside. Nevertheless, further validation studies are needed in the future.