The 1990 Clean Air Act mandated oxygenation of gasoline in regions where carbon monoxide standards were not met. To achieve this standard, methyl tertiary butyl ether (MTBE) was increased to 15% by volume during winter months in many locations. Subsequent to the increase of MTBE in gasoline, commuters reported increases in symptoms such as headache, nausea, and eye, nose, and throat irritation. The present study compared 12 individuals selected based on self-report of symptoms (self-reported sensitives; SRSs) associated with MTBE to 19 controls without self-reported sensitivities. In a double-blind, repeated measures, controlled exposure, subjects were exposed for 15 min to clean air, gasoline, gasoline with 11% MTBE, and gasoline with 15% MTBE. Symptoms, odor ratings, neurobehavioral performance on a task of driving simulation, and psychophysiologic responses (heart and respiration rate, end-tidal CO(2), finger pulse volume, electromyograph, finger temperature) were measured before, during, and immediately after exposure. Relative to controls, SRSs reported significantly more total symptoms when exposed to gasoline with 15% MTBE than when exposed to gasoline with 11% MTBE or to clean air. However, these differences in symptoms were not accompanied by significant differences in neurobehavioral performance or psychophysiologic responses. No significant differences in symptoms or neurobehavioral or psychophysiologic responses were observed when exposure to gasoline with 11% MTBE was compared to clean air or to gasoline. Thus, the present study, although showing increased total symptoms among SRSs when exposed to gasoline with 15% MTBE, did not support a dose-response relationship for MTBE exposure nor the symptom specificity associated with MTBE in epidemiologic studies.