Methyl tertiary butyl ether was evaluated for acute inhalation neurotoxicity in rats (22/sex/group) exposed for 6 hours to target concentrations of 0, 800, 4000, or 8000 ppm. Motor activity was evaluated before and after exposure using an automated device. Neurobehavioral function was assessed prior to and after exposure using a functional observation battery (FOB). Dose-related FOB findings were noted at 4000 and 8000 ppm, and clear motor activity changes were seen in the 8000 ppm group. The pattern and time course of these were indicative of transient CNS sedation. A 13- week repeated vapor inhalation/neurotoxicity study was conducted in rats (25/sex/group) exposed for 6 hours/day, 5 days/week to 0, 800, 4000, or 8000 ppm MTBE. Transient ataxia was noted in high-dose rats, and elevated body temperature occurred at 4000 ppm and higher. Depressed body weight gain was seen in males at 4000 ppm and above, and in females at 8000 ppm. No mortalities nor treatment-related gross or histopathological lesions were found at any exposure level. No adverse effects were noted at 800 ppm. MTBE induced mild toxicity, but did not appear to be a neurotoxicant under the conditions of this study.