Figure 2. Plates from the seventh book of the first edition (1543) of the Fabrica by Andreas Vesalius, showing what is believed to be the oldest anatomical drawings in Western literature of the hypothalamic-pituitary unit. (Courtesy of the Library of the Department of Human Anatomy of the University of Bologna, Italy, with permission) 1) Enlarged view of the pituitary gland (A), hypothalamic infundibulum (B) and ducts comprising the foramen lacerum and superior orbital fissure (C, D, E, F) believed to drain brain mucus or phlegm (in Latin pituita) from the pituitary gland to the nasopharynx; 2) anatomical relationships between the infundibulum (E), the dural diaphragma sellae (F), the internal carotid arteries (C, D) and oculomotor nerves (G), all seen from above and, thus ventral to the posterior clinoid processes of the sella turcica (A, B); 3) composite image including a) an enlarged view of the rete mirabilis formed as a reticular plexus by the carotid arteries entering (A, B) and emerging (C, D) around the pituitary gland (E); b) detailed view of the reticular plexus arising from the carotids (B, C) on each side of the pituitary (A); 4) anatomy of the arterial, vertebral (dorsal vessels, F) and common carotid (ventral vessels, E) systems: the rete mirabilis (B) is provided by the internal carotid artery (D), branching medially with respect to the external carotid artery (C). Note that Vesalius portrayed the rete mirabilis widening symmetrically and superiorly (A) to vascularize the area of the infundibulum and hypothalamic floor, anticipating our current knowledge of the circuminfundibular and prechiasmal arteriolar-capillary plexus; 5) anatomy of the venous vertebral (D) and internal jugular (C) systems, including the common facial vein (D). Note the X-shaped, venous pattern at the center of the image, pointing to the area of the rete mirabilis: it is provided by four symmetrical branches of the internal jugular vein, and recapitulates the distribution of the inferior and superior petrosal, and spheno-parietal sinuses around the cavernous sinus. Thus, this drawing can be considered the first demonstration of a venous route from the pituitary through the internal jugular system, exploited for sampling of pituitary hormonal secretions only in the 2nd half of the 20th century. (From Toni R., Ancient views on the hypothalamic-pituitary-thyroid axis: an historical and epistemological perspective, Pituitary 3: 83-95, 2000, and Toni R. “Il sistema ipotalamo-ipofisario nell’antichità [The hypothalamic-pituitary system in the antiquity] – Dedicato alla memoria del Prof. Aldo Pinchera [Dedicated to the memory of Prof. Aldo Pinchera], In: L’Endocrinologo, Per una Storia dell’Endocrinologia [For a History of Endocrinology], 13, suppl. to n. 6, 1-11, 2012.