Responses of segments of basilar and middle cerebral arteries of eight human infants to activation of perivascular nerves and to vasoactive drugs were studied using a resistance artery myograph. The infants ages ranged from 23 wk of gestation to 34 postnatal days. Neurogenic vasoconstriction occurred in all segments and at 8 Hz was 12.7 ± 3.5% (11%) of tissue maximum and was blocked by phentolamine (10-6 M). There was no evidence of a neurogenic dilator response. Catecholamine histofluorescence was seen in nerves in the adventitia at all ages studied. Norepinephrine ED50 was 7.6 ± 1.8 × 10-7 M, and its maximum effect was 43.1 ± 5.7% of tissue maximum. Both neural and norepinephrine responses were greater than those of the proximal parts of adult human middle cerebral arteries obtained postmortem and surgically removed adult human pial arteries. Electron microscopy demonstrated that neural density at the adventitiomedial junction in the infant vessels was greater than in the pial arteries. Constrictor responses to serotonin and prostaglandin F2α were minimal in the two infants of 23 and 24 wk of gestation but were clearly present in the older infants. Histamine and acetylcholine were potent vasodilators. Indomethacin potentiated agonist-induced contraction. In a limited number of trials angiotensin II, neuropeptide Y, caused contraction and bradykinin, relaxation. It is concluded that there is a quantitative similarity between the studied responses of infant cerebral artery segments and human pial arteries of similar diameter. However, sympathetic nerves may potentially play a more important role in the regulation of cerebrovascular tone in the infant compared with the adult, and during the gestational period examined these vessels possess an indomethacin-sensitive system that buffers agonist tone.