Percutaneous nicotine administration induces predominant sudorific and rubiform responses in the skin which may be accompanied by subtle piloerection, hyperalgesia and pruritus (although these signs are not overtly manifest). These dermal responses are complex and mechanisms have been proposed for the direct nicotine-stimulation of sweat glands, piloerection and vasoconstriction. These reactions are accompanied by secondary activation and release of vasodilator peptides which produce a predominating vasodilator tone following topical administration, this response masking the direct axon reflex-mediated vasoconstriction.