Regional differences in the proximal part of mouse epididymis were reported to provide a morphological baseline for studies on functional zonation of this part that is critical in sperm maturation. Macroscopical, histological, ultrastructural, and histochemical observations permitted us to subdivide this part into five segments, characterized by epithelial height, nuclear position, cytological and histochemical features of principal cells. Segment I corresponded to the initial segment previously described in rodents. Segment II differed from segment I by endoplasmic reticulum (ER) and dictyosomes aspect in principal cells, apical alkaline phosphatase and Ca2+-dependent ATPase activities. Segment III was characterized by spermatozoa package, high content of cells in multivesicular bodies, mitochondria shape, complex interdigitating membranes, and strong periodic acid-Schiff (PAS)-positive cell border. Segments IV and V presented the same cytological features but differed by their esterase activity. In the principal cells of each segment, dense spherical concretions were scattered in ER caveolae. Cells with apical nuclei were classified into two groups. The cells of the first group presented the same morphological and histochemical features as the adjacent principal cells and were scattered in the five segments ("apical cells"). The cells of the second group differed from the others by their goblet shape, a dense cytoplasm, and a high mitochondria succinate-D activity. They presented different cytological and histochemical features depending on their localization in segments I ("narrow cells"), II ("prominent cells"), or III, IV, V ("mitochondria goblet-cells"). The possible relationships between epithelium structure and epididymal functions were herein discussed.