We have developed and demonstrated an imaging system that couples an X-ray CT scanner to a scintillation camera for the localization and absolute measurement of radionuclide uptake. We use the registered CT images to provide physical information to overcome the quantitative errors in nuclear imaging due to attenuation, scattering and limited spatial resolution. The registration accuracy and precision in phantom experiments was 0.0/spl plusmn/0.4 mm. Preliminary patient scans suggest that the registration techniques developed for phantom studies can be used. Conversion of X-ray CT image data to attenuation maps was accomplished by the scaling of calibration data and includes extensions to account for the presence of iodinated contrast agents. Experimental phantom studies with /sup 99m/Tc show absolute quantitation with less than 10% error for up to 2:1 target:background activity concentration for objects as small as 2.7 ml. We are currently evaluating the imaging methods for the localization and absolute quantitation of /sup 131/I-MIBG (metaiodobenzylguanidine) in neuroblastoma patients.