A method for achieving quantitative single-photon emission computed tomography (SPECT) based upon corrections derived from x-ray computed tomography (CT) data is presented. A CT-derived attenuation map is used to perform transmission-dependent scatter correction (TDSC) in conjunction with non-uniform attenuation correction. The original CT data are also utilized to correct for partial volume effects in small volumes of interest. The accuracy of the quantitative technique has been evaluated with phantom experiments and clinical lung ventilation/perfusion SPECT/CT studies. A comparison of calculated values with the known total activities and concentrations in a mixed-material cylindrical phantom, and in liver and cardiac inserts within an anthropomorphic torso phantom, produced accurate results. The total activity in corrected ventilation-subtracted perfusion images was compared to the calibrated injected dose of [99mTc]-MAA (macro-aggregated albumin). The average difference over 12 studies between the known and calculated activities was found to be -1%, with a range of ±7%.