Brush cells have been identified in the respiratory and gastrointestinal tract mucosa of many mammalian species. In humans they are found in the respiratory tract and the gastrointestinal apparatus, in both the stomach and the gallbladder. The function of brush cells is unknown, and most morphological data have been obtained in rodents. To extend our knowledge of human brush cells, we performed an ultrastructural investigation of human small intestine brush cells. Six brush cells identified in five out of more than 300 small intestine biopsies performed for gastrointestinal tract disorders were examined by transmission electron microscopy. Five brush cells were located on the surface epithelium and one in a crypt. The five surface brush cells were characterized by a narrow apical pole from which emerged microvilli that were longer and thicker than those of enterocytes. The filamentous core extended far into the cell body without forming the terminal web. Caveolae were abundant. Filaments were in the form of microfilaments and intermediate filaments. Cytoplasmic projections containing filaments were found on the basolateral surface of brush cells. In a single cell, axons containing vesicles and dense core granules were in close contact both with the basal and the lateral surface of the cell. The crypt brush cell appeared less mature. We concluded that human small intestine brush cells share a similar ultrastructural biology with those of other mammals. They are polarized and well‐differentiated cells endowed with a distinctive cytoskeleton. The observation of nerve fibres closely associated with brush cells, never previously described in humans, lends support to the hypothesis of a receptor role for these cells.