The kinetic behavior of Tc-99m-ethyl cysteinate dimer (Tc-99m-ECD) in the human brain was investigated in six normal volunteers, Methods: Dynamic SPECT and a three-compartmental model were used to estimate the rate constants of Tc-99m-ECD in normal human brain. Extraction fraction (E), retention fraction (R) and permeability surface area product (PS product) of Tc-99m-ECD were calculated using the rate constants, Regional cerebral blood flow (rCBF) was measured by PET with O-15-water, Results: The rate constants in the cerebral cortex were estimated as 0.307 +/- 0.021 for K1 (influx constant), 0.201 +/- 0.047 for k2 (backdiffusion rate constant), 0.547 +/- 0.103 for k3 (lipophilic-to-hydrophilic conversion constant) and 0.0028 +/- 0.0012 for k5 (rate constant from lipophilic compartment to blood) al rCBF of 0.509 +/- 0.055 ml/g/min (mean +/- s.d.), The first-pass extraction, retention fraction and PS product were calculated as 0.608 +/- 0.069, 0.734 +/- 0.047 and 0.477 +/- 0.060, respectively. The first- pass extraction of Tc-99m-ECD decreased significantly with increases in rCBF, The retention fraction and PS product of Tc-99m-ECD did not show significant changes within the normal range of rCBF. The net extraction of (99m)c-ECD calculated from the static SPECT image obtained from 20 to 40 min was 0.358 +/- 0.039 in the cortex. Conclusion: Technetium-99m-ECD has a fairly high brain extraction, and its retention fraction and PS product appear to be independent of rCBF in the healthy human brain.