A study was conducted to evaluate the feasibility of simultaneous dual radionuclide brain imaging with 123I and 99mTc using photopeak image subtraction techniques or offset photopeak image acquisition. The contribution of the photons from one radionuclide to a second radionuclide's photopeak energy window (crosstalk) was evaluated for SPECT and planar imaging of a brain phantom containing 123I and 99mTc for a range of activity levels and distribution properties approximating those in rCBF images of the adult human brain. Crosstalk was evaluated for 10% symmetrical energy windows centered on the 123I and 99mTc photopeaks and for 10% energy windows asymmetrically placed to the left and right of the center of the respective photopeaks. Major observations include: (1) in the centered photopeak windows, 99mTc crosstalk in the 123I window is 8.9% of the 99mTc seen in the 99mTc window and ranges from 37.5% to 75.0% of the 123I in the 123I window. 123I crosstalk is 37.8% of the 123I seen in the 123I window and ranges from 4.4% to 8.9% of the 99mTc seen in the 99mTc window; (2) the spatial distribution of a radionuclide's crosstalk photons differs from that observed in the radionuclide's photopeak window; (3) a 99mTc photopeak window offset to the left does not decrease 123I crosstalk, and the percentage of 99mTc scattered photons is significantly increased in the window.(ABSTRACT TRUNCATED AT 250 WORDS)