General anesthesia may result from interruption of neural transmission in descrete areas of brain rather than from a generalized depression of transmission. Preliminary experiments have demonstrated that anesthetics selectively alter neurotransmitter concentrations, or glucose metabolism, in specific regions in the brain. The authors questioned whether anesthetic requirement would be altered by destruction of selected nuclei. They found that bilateral destruction of a large norepinephrine cell-body area, the locus coeruleus in the rat, decreased halothane MAC from 1.13 to 0.78 per cent (P ≤ 0.01) and cyclopropane MAC from 20.5 to 16.1 per cent (P ≤ 0.001) compared with sham-operated littermates of equal weight. Ablation of the locus coeruleus did not change hypothalamic norepinephrine content, but decreased cortical norepinephrine levels by 80 per cent. Destruction of the ventral bundle, which supplies approximately 40 per cent of the norepinephrine in the central gray catecholamine area, decreased halothane MAC 35 per cent (P ≤ 0.001) and cyclopropane MAC 16 per cent (P ≤ 0.01 ). However, rats that had ventral-bundle lesions weighed 18 per cent less (P ≤ 0.001) than controls. Ventral-bundle lesions decreased hypothalamic norepinephrine by 85 per cent without altering cortical norepinephrine. Lesions in the serotonin-rich nucleus raphe dorsalis decreased halothane MAC 25 per cent (P ≤ 0.02) and cyclopropane MAC 16 per cent (P ≤ 0.01 ). These lesions decreased hypothalamic serotonin content by 40 per cent, and cortical serotonin content by 80 percent. Although destruction of individual nuclei significantly decreased anesthetic requirement, lesions in no one area altered MAC by more than 35 per cent. The hypothesis that general anesthesia results from discrete rather than generalized depression of transmission is thus supported, but not proven, by these experiments.