INTRODUCTION Dosimetric studies for targeted radiotherapy require the quantification of activity from scintigraphic images. Quantitative imaging is difficult to achieve because of several effects that can lead to errors in activity estimates, some of which are more apparent when I-131 is considered as a source. An evaluation of these phenomena was performed by modeling the gamma camera and its behavior using Monte Carlo simulations. Two gamma cameras were modeled: DST-XLi and Millennium VG Hawk-Eye (GEMS), and two Monte Carlo codes were used: MCNP (LANL) and GATE (openGate collaboration). GATE is a dedicated single photon emission computed tomography/positron emission tomography (SPECT)/(PET) software based on Geant4 (CERN, Geneve). MATERIALS AND METHODS Gamma-camera modeling was performed in 2 steps: first without a collimator, then with a high-energy, all-purpose (HEAP) collimator according to the specifications given by the manufacturer (the simulation took the hexagonal shape of collimator holes into account). Simulated and measured energy spectra from point sources in air were compared (with or without a collimator). Spatial resolution was obtained from line sources in air at various distances from the detector heads. The photons detected in the 20% energy window from a point source were analyzed in order to determine the amount of primary photons, scattered photons (in the collimator), and septal photons (i.e., photons that crossed the collimator septa without interacting). RESULTS Both codes agree well with experimental measurements for the two gamma cameras considered in this study. This allowed us to validate gamma-camera modeling and also served as a benchmark of GATE (new code) versus MCNP (reference code). As shown previously by Dewaraja et al., septal penetration is an important source of image degradation when HEAP collimators are used for I-131 imaging. With the DST-XLi, and for a point source in air, our simulations have shown that 53% of scattered (30%) and septal penetration (23%) photons are detected in the 20% window. CONCLUSION The modeling of two gamma cameras (DST-XLi and Millennium VG Hawk-Eye) has been performed with two Monte Carlo codes (MCNP and Gate). Results obtained with the two Monte Carlo codes agree well with experimental results. As already indicated by several authors, septal penetration and scattered photons in the collimator have a major impact on I-131 scintigraphic imaging.