|The pathophysiology of tennis elbow is not clearly understood, but there is general agreement that the extensor carpi radialis brevis (ECRB) muscle plays a central role in the development of this disease. Previous histopathological studies have mainly been focused on the most painful area at the proximal ECRB tendon. The basis for this investigation was that the ECRB muscle, its proximal and distal tendons, and the joints interact as a functional unit to produce joint rotation or torque. Therefore, to further understand aetiological factors, the biomechanical properties of the wrist extensor muscles, the structural condition of the ECRB muscle tissue and the preconditions for pain production and nerve-mediated effects at the muscle origin were investigated.Changes in sarcomere length, as a function of joint angle, were measured using intraoperative laser diffraction. There was a significant effect of wrist flexion and ulnar deviation but not forearm pronation. The axes of forearm rotation and wrist radial-ulnar deviation seem to act independently, since no statistical interaction occurred between these movements. A most unexpected result was a biphasic length-tension relationship during elbow joint rotation. The two lengthening phases imply eccentric contractions of the active ECRB muscle. Eccentric muscle contractions are known to result in increased levels of tension and may predispose to muscle damage. The results suggest that wrist and forearm movements are associated with the types of actions that cause tennis elbow but that high force spikes following the cyclic lengthening and shortening of the ECRB during monotonic elbow flexion/extension may be a causative factor in the development of this disease. Biopsy specimens from the ECRB muscle were analysed by enzyme- and immunohistochemical methods. Morphological abnormalities were significantly more frequent in tennis elbow patients than in controls and included fibre necrosis, signs of muscle fibre regeneration, an uneven distribution of mitochondrial enzyme activity and a conversion of fibre types to more oxidative forms. These changes may, directly or indirectly, reflect the cumulative effect of mechanical and/or metabolic overload and that decreased muscular performance in patients with tennis elbow may be due to both elbow pain and physical damage to the ECRB muscle.No inflammatory cell infiltrates were seen in sections from biopsy specimens from the proximal tendon insertion in tennis elbow patients and only very few solitary mast cells were observed. The results provide further supporting evidence for previous suggestions that tennis elbow is not an inflammatory process in the sense of involving inflammatory cells.The innervation at the ECRB muscle origin was investigated using immunohistochemical techniques and antibodies to various nerve markers. There was a vasoconstrictor sympathetic innervation in the walls of a subpopulation of the arterioles, no vasodilator sympathetic nerve fibres and a sensory innervation restricted to a subpopulation of the small blood vessels. Thus, there appears to be an imbalance between the vasoconstrictor and vasodilator innervation along the vascular tree in this region. There was a similar pattern of innervation in the patients and the controls. Sensory nerves contain the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP). It is a well-known fact that SP and CGRP can have various important efferent effects, including microvascular leakage and local oedema formation. The observations constitute a structural basis for pain perception and a morphological substrate for possible efferent effects from sensory and sympathetic innervation at two different sites along the vascular tree at the ECRB muscle origin.