Immunohistochemical studies showed that substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity co-exist in capsaicin-sensitive primary sensory neurons. Varicose SP- and CGRP-immunoreactive nerve fibres with a similar distribution pattern were seen in the lower airways and heart. The functional analysis revealed that CGRP caused cardiac stimulation and had, together with SP and neurokinin A, potent hypotensive effects. Vascular permeability was increased by SP and neurokinin A, and the bronchial smooth muscle was particularly sensitive to neurokinin A. Thus, multiple peptides stored in an possible released from the same nerve endings by capsaicin may exert differential effects in various target tissues.