This study was undertaken to determine if long-term hyposensitization causes late sequelae, particularly those reflecting aberrant immunologic responses. Atopic individuals receiving five or more years of hyposensitization with allergenic extracts showed no increased autoimmune, collagen vascular, or lymphoproliferative disease. In addition, chronic hyposensitization did not have adverse effects on immunologic reactivity as assessed by a number of immune parameters. Particularly noteworthy was the absence of immune complexes in the serum of patients undergoing long-term hyposensitization. This study represents the first systematic investigation of potential adverse effects of long-term hyposensitization.