With use of immunohistochemistry and antibodies to substance P and calcitonin gene-related peptide, nerve fibers showing substance P-like and calcitonin gene-related peptide-like immunoreactivity were demonstrated at the origin of the extensor carpi radialis brevis muscle in patients with tennis elbow (n = 6) and in healthy controls (n = 6). The nerve fibers were distributed in association with a subpopulation of small blood vessels and in nerve bundles but were not distributed in the tunica media-adventitia junction of the arterioles. There were no inflammatory-cell infiltrates and few solitary mast cells. The present study gives further evidence to previous suggestions that tennis elbow is not an inflammatory process in the sense of involving inflammatory cells. Frequent mechanical involvement affects sensory innervation, and substance P and calcitonin gene-related peptide may have various important efferent effects, including microvascular leakage and local edema formation; therefore, the observations from this study constitute a morphological substrate for possible effects of substance P and calcitonin gene-related peptide at the origin of the extensor carpi radialis brevis muscle.