The single photon emission computed tomography (SPECT) radiotracer [¹²³I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B′_max). To evaluate the ability of such indices in accurately accessing the B′_max the authors compared them with absolute values of B′_max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [¹²³I]iomazenil and estimated the total and specific distribution volumes (DV_{T SPECT}, DV_{S SPECT}) and the binding potential (BP) using unconstrained (BP_SPECT) and constrained (BP_{C SPECT}) compartmental models. For PET studies, the authors used a multiinjection approach with [¹¹C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B′_max, and some other binding parameters. The authors studied the correlation of different binding parameters with B′_max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B′_max and the DV_PET were highly correlated (r = 0.988). This confirms that it is possible to use the DV_PET to access benzodiazepine receptor density. For SPECT data, the correlation between DV_SPECT estimated using a two-and three-compartment model was also high (r = 0.999). The DV_{T SPECT} and BP_{C SPECT} parameters estimated with a constrained three-compartment model or the DV_T″_SPECT parameter estimated with a two-compartment model were also highly correlated to the B′_max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.