A comprehensive examination was made, which included histological, electron microscopic and chromatographic mass spectrometric studies of biological specimens obtained from 18 patients with leg lymphedema. The development of lymphedema was found to accompanied by the specific connective tissue structure being formed along with the presence of low-differentiated and necrotic areas associated with the cytopathology of blood and lymph vessels and impaired microcirculation. The connective tissue areas under study were demonstrated to have a pronounced antigenicity and aggressive properties against other tissues and structures. The morphological changes revealed are directly related to the impaired metabolism of protein, fatty acids, and complex polysaccharides.