It has been hypothesized that acute lesions of the brain enlarge through an autodestructive process. Serotonin (5HT), a potent cerebral vasoconstrictor, is believed by some to mediate the process by reducing cerebral blood flow (CBF) in tissue surrounding the lesion. The hypothesis was tested in cynomologus monkeys anesthetized with ketamine and nitrous oxide. Craniectomies, 7 mm in diameter, were performed in each parietal area. The dura was opened and polarographical electrodes of thin platinum wire were inserted into the parietal lobe cortex of each hemisphere. Mock cerebrospinal fluid (CSF) was irrigated continously onto the brain surrounding the electrodes, from which local CBF was determined repeatedly by the hydrogen-clearance technique. After baseline CBF was established, solutions of 5HT in mock CSF (in concentrations of 5 X 10(-7) M, 5 X 10(-5) M, and 5 X 10(-3) M) were irrigated onto one hemisphere while the opposite hemisphere served as control. 5HT failed to change CBF. Although 5HT is a potent vasoconstrictor, under physiologic conditions it apparently is unable to effect hemodynamically significant constriction of the peripheral cerebral vasculature of the anesthetized monkey brain.