Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 degrees), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC + AT) and (SC + CBC + AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (% ID/100 ml) obtained after (SC + CBC + AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123I-epidepride uptake using SPET has been developed which can be directly applied to other 123I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.