Recombinant adeno-associated virus serotype 2 (rAAV2) vectors have been shown to deliver genes effectively to neurons in the brain, retina, and spinal cord. The characterization of new AAV serotypes revealed different patterns of transduction in a diverse array of tissues (Gao, G., Vandenberghe, L.H., and Wilson, J.M. [2005]. Curr. Gene Ther. 5, 285-297). Here, we extensively compare the neural tropism of human-derived rAAVs (types 2/1, 2, and 2/5) with nonhuman primate-derived rAAVs (types 2/7 and 2/8) in adult mouse brain. Mice were injected with rAAV type 2/1, 2, 2/5, 2/7, or 2/8 via the caudate-putamen and substantia nigra. Intrahippocampal injections were also performed for rAAV2/7 and rAAV2/8. In all regions injected, the vectors transduced neurons almost exclusively. Retrograde transduction of all rAAV pseudotypes was also observed in particular CNS areas. At high titers, all rAAV pseudotypes transduced comparable brain volumes in all targeted regions except for rAAV2, which transduced much smaller brain volumes. A dose-range comparison of intrastriatally injected rAAV types 2/5, 2/7, and 2/8 highlighted that the transduction efficiency, as determined by transduced volume and biophotonic imaging of green fluorescent protein expression intensity, was significantly higher for rAAV2/5 and rAAV2/7 compared with rAAV2/8 at low titers, whereas all three serotypes performed equally well at higher doses. These results demonstrate the use and efficiency of both human- and nonhuman primate-derived rAAV vectors for disease modeling and their potential for gene therapy.