Skin homografts were performed in seven patients with connective tissue disorders who were undergoing lymphocyte depletion by prolonged thoracic duct drainage. In six patients who had been adequately depleted of lymphocytes, a substantial prolongation of homograft survival occurred, based on data reported in the literature for normal control subjects. In one patient, immunologic tolerance to a D-match skin homograft developed, whereas the other patients showed only prolonged survival of the homografts. The data suggest that both enhanced homograft survival and development of immunologic tolerance occur as a consequence of prolonged thoracic duct drainage.