Gray and white matter were obtained during neurosurgical therapy of focal epilepsy from 17 patients. In 10 patients, receiving only phenobarbital, the drug was uniformly distributed between gray and white matter. Phenytoin concentrations averaged 1.4-fold greater in white matter than in gray matter when expressed per gram wet weight of tissue. The gray matter/plasma ratio of phenytoin was approximately 2-fold greater than that of phenobarbital. Carbamazepine levels were also slightly greater in white matter The data revealed wide differences between drugs in the relative concentrations in gray and white matter, which must be taken into account in any quantitative studies of anticonvulsant drug levels in the brain.