Aspartame is an o-methyl ester composed of phenylalanine and aspartic acid. After its jnal approval as a sweetener in 1981 1 a number of reports of adverse reactions to aspartame appeared in the literature. To explore the pathogenesis of such reactions, we initiated a study in July 1986 to identify subjects with hypersensitivi8 reactions to aspartame with blinded challenge procedures. The study was closed after 32 months. During that time, we advertised in local newspapers and worked closely with the local community of allergists and dermatologists in an attempt to recruit subjects with hypersensitivity reactions to aspartame. A total of 61 self-referrals and physician referrals were screened, with 20 referrals evaluated in clinic. After this evaluation, 12 patients underwent single-and double-blind challenge with up to 2000 mg of aspartame. No subject with a clear& reproducible adverse reaction to aspartame was ident$ed. In summary. we found that it is d@cult to recruit study subjects with a history of hypersensitivity reactions to aspartame and that subjects who believed themselves allergic to aspartame did not have reproducible reactions. (J ALLERGY CLIN IMMUNOL 1991;87:821-7.) Aspartame is an o-methyl ester composed of phenylalanine and aspartic acid. It was discovered serendipitously in 1965 by a chemist working to find an inhibitor of gastrin with possible applications as an antiulcer agent.' In 1973, G. D. Searle petitioned the FDA for its approval to market aspartame as a sweetener.' In 1974, aspartame was approved for use in dry foods. In December 1975, the FDA stayed the approval for marketing aspartame because of concern over problems noted in studies by Searle Laboratories (Chicago, Ill.) and because of allegations that aspartame was unsafe and could cause mental retardation and endocrine dysfunction. In July 1981, the FDA Commissioner reapproved aspartame as a food additive, and marketing was started that same year. In July