Summary 1. The effects of L-leucine, L-valine, L-phenylalanine, alpha-ketoisocaproic acid, alpha-ketoisovaleric acid, phenylpyruvic acid, and phenylacetic acid on oxygen consumption by slices or homogenates of rat brain were measured. 2. None of these substrates significantly inhibited oxygen uptake by rat brain homogenates. 3. L-leucine, L-valine, and L-phenylalanine were also found not to significantly depress oxygen uptake by brain slices. 4. On the other hand, alpha-ketoisocaproic acid, alpha-ketoisovaleric acid, phenylpyruvic acid, and phenylacetic acid (at concentrations of 0.01 sc > m did depress oxygen utilization by brain slices to the extent of 10-27% of control values. 5. It is suggested that the central nervous system dysfunction observed in patients with certain hereditary diseases characterized by defects in amino acid metabolism may be related to the accumulation of alpha-ketoacids which occurs in these diseases.