Capsaicin has been shown to specifically deplete substance P from primary sensory afferents, including sensory nerves innervating blood vessels of the cerebral circulation as well as other vascular beds. In order to further document the specificity of this treatment, we examined the effect of capsaicin treatment on 3 other types of nerves in the guinea pig. Four tissues were examined: cerebral arteries, the mesenteric artery, the heart and iris. Norepinephrine content was not altered after capsaicin treatment, confirming that adrenergic nerves are unaffected. As indices of cholinergic nerves, activities of choline acetyltransferase and acetylcholinesterase were also unchanged after capsaicin treatment. In addition, no significant differences in levels of vasoactive intestinal peptide in cerebral arteries and the heart were found in animals treated with capsaicin. These findings underscore the specificity of capsaicin treatment for substance P containing nerves.