The lumped constant defined as the conversion factor between the net uptake of fluoro-2-deoxy-D-glucose (FDG) and glucose was calculated from global CMRglc and from positron emission tomography (PET) using FDG as tracer (CMRFDG). Fifteen healthy, normal volunteers (mean age 24 +/- 4 years) were studied. Global CBF and CMRglc were measured with the Kety-Schmidt technique using 133Xe as tracer, and values were corrected for errors from incomplete diffusion equilibrium for inert gas tracer between brain tissue and cerebral venous blood. Measurements of CMRFDG were obtained with PET using the dynamic and single-scan methods and the K1-k3 model. Measurements with the Kety-Schmidt technique and PET-FDG were performed simultaneously. Global CBF was 47.1 +/- 8.0 mL.100 g-1.min-1, and CMRglc was 22.8 +/- 4.1 mumol.100 g-1.min-1. No difference in CMRFDG was found with the two methods (17.8 +/- 1.6 and 18.2 +/- 1.3 mumol .100 g-1.min-1, dynamic and single scan methods, respectively). Accordingly, the lumped constant ranged from 0.80 +/- 0.16 to 0.82 +/- 0.15, with a mean value of 0.81 +/- 0.15. The mean ratio between phosphorylation of FDG and glucose (k3*/k3) was 0.39 +/- 0.25. The discrepancy between the lumped constant determined in this study and previously obtained values can be explained partly by methodologic problems, and we conclude that most of the discrepancy results from previous overestimation of global CBF.