Striatal interneurons display a morphological and chemical heterogeneity that has been particularly well characterized in rats, monkeys and humans. By comparison much less is known of striatal interneurons in mice, although these animals are now widely used as transgenic models of various neurodegenerative diseases. The present immunohistochemical study aimed at characterizing striatal interneurons expressing calretinin (CR) in mice compared to those in squirrel monkeys and humans. The mouse striatum contains both small (9-12 μm) and medium-sized (15-20 μm) CR+ cells. The small cells are intensely stained with a single, slightly varicose and moderately arborized process. They occur throughout the striatum (77±9 cells/mm(3)), but prevail in the area of the subventricular zone and subcallosal streak, with statistically significant anteroposterior and dorsoventral decreasing gradients. The medium-sized cells are less intensely immunoreactive and possess 2-3 long, slightly varicose and poorly branched dendrites. They are rather uniformly scattered throughout the striatum and three times more numerous (224±31 cells/mm(3)) than the smaller CR+ cells. Double immunostaining experiments with choline acetyltransferase (ChAT) as a cholinergic marker in normal and Drd1a-tdTomato/Drd2-EGFP double transgenic mice reveal that none of the small or medium-sized CR+ cells express ChAT or D1 and D2 dopamine receptors. In contrast, the striatum in human and nonhuman primates harbors small and medium-sized CR+/ChAT- cells, as well as large CR+/ChAT+ interneurons that are absent in mice. Such a difference between rodents and primates must be taken into consideration if one hopes to better understand the striatal function in normal and pathological conditions. Copyright © 2014 Elsevier B.V. All rights reserved.