The premamillary artery was studied in 50 unfixed human brain hemispheres (51 vessels were found) which were injected with polyester resin and dissected under the operating microscope. In one hemisphere there was duplication of the premamillary artery. There were premamillary arteries arising from the posterior communicating artery (PCoA) in 49 cases and from the posterior cerebral artery in the remaining two. The arteries originated from the superior and lateral surfaces of the PCoA and coursed superiorly, laterally, and posteriorly to enter a triangular perforated space limited by the mamillary body and tuber cinereum medially, the optic tract anterolaterally, and the cerebral peduncle posterolaterally. This space is called the paramedian perforated substance. The premamillary artery had an outer diameter of 0.6 +/- 0.2 mm on the right side and 0.6 +/- 0.1 mm on the left. The length of the premamillary artery was 12.0 +/- 2.0 mm on the right side and 12.7 +/- 1.9 mm on the left. Sixty-three percent of the premamillary arteries gave off branches that supplied the cerebral peduncles, optic tract, and paramedian perforated space. The clinical importance of these anatomical data in the symptomatology and management of vascular and neoplastic diseases in and around the posterior circle of Willis is discussed.