Effects of capsaicin in vivo and in vitro on calcitonin gene-related peptide (CGRP)-containing nerves were examined in cerebral arteries. CGRP-like immunoreactive (CGRP-I) nerves were demonstrated in cerebral arteries of rats, guinea pigs and rabbits. The overall distribution of CGRP-I nerves was similar to that of substance P-containing nerves. Since the distribution of CGRP-I nerves of cerebral arteries among these species was the densest in guinea pigs, this animal was used to study the effect of several treatments on CGRP-I nerves. Catecholamine (CA)-fluorescence but not CGRP-I nerves was abolished by surgical sympathectomy or reserpine pretreatment. Pretreatment of the animal with capsaicin abolished CGRP-I nerves of cerebral arteries. CGRP-like immunoreactivity disappeared from cerebral arteries by in vitro incubation with capsaicin. Capsaicin treatment in vivo and in vitro did not affect CA-fluorescence nerves in these arteries. Since capsaicin selectively affects primary afferent nerves, it is suggested that CGRP is contained in sensory nerves. Capsaicin may be a valuable tool in elucidating the physiological or pathophysiological role of CGRP in cerebral circulation.