Background: Questions have been raised since the early 1980s about monosodium glutamate (MSG) and provocation of asthma. Because MSG is widely available as a chemical in both natural foods and as an additive in many prepared foods, the need to define the relationship of MSG to asthma is of great importance. Objective: The purpose of this study was to determine whether MSG ingestion induces asthma attacks in asthmatic subjects. Methods: With single-blind, placebo-controlled screening challenges, 100 subjects with asthma (30 subjects with a history of Oriental restaurant asthma attacks; 70 subjects with a negative history) were challenged with 2.5 g of MSG. A total of 78 patients were proved to have aspirin-sensitive asthma. Results: No patient had a significant fall in FEV₁ value or the development of asthma symptoms during the MSG challenge. The mean change in FEV₁ with MSG challenge was no different from that of placebo challenge. Subjects with an MSG-positive history showed no significant percent decrease in FEV₁ values after placebo challenges compared with MSG 2.5 g oral challenge (P = .28). In the group with an MSG-negative history, there was no statistical difference in the change in lowest FEV₁ values between the placebo and MSG challenges (P = .44). The exact 1-sided 95% confidence interval (CI) for the probability of MSG sensitivity in individuals with aspirin-sensitive asthma (negative history) is 0% to 0.04%. When combined with previous studies that did not demonstrate MSG-provoked asthma, the 95% CI is 0% to 0.03%. For patients with an MSG-positive history, the exact 1-sided 95% CI for the probability of MSG sensitivity in this study was 0% to 0.07%, which is somewhat wider because of the smaller sample size. Conclusions: MSG challenges in subjects with and without a perceived sensitivity to MSG failed to induce signs or symptoms of asthma. Therefore in view of the poorly conducted studies that proposed that MSG induced asthma and the subsequent studies that failed to confirm those findings, it is important to maintain a healthy skepticism about the existence of MSG sensitivity in individuals with asthma. (J Allergy Clin Immunol 1999;104:305-10.)