The permeability of human thoracic and lumbar dura mater to various compounds in clinical use was determined in vitro. Sections of dura mater, 3 to 4 cm in diameter, obtained at post-mortem were placed between the ports (area = 3 cm2) of two glass chambers (A and B) which fitted tightly together to form a two-chamber apparatus for measuring permeability through the dura. Each chamber contained 5 ml of artificial cerebrospinal fluid. A sample of test drug solution was introduced into one chamber (A) and 50 microliters aliquots were withdrawn from the other chamber (B) at predetermined intervals. Permeability was determined by calculating the rate of diffusion (slope) from the plot of mean drug concentration (chamber B) versus time. Dura mater permeability was shown to be a simple diffusion process and to be independent of lipid-solubility and molecular weight. Permeability appeared to increase with age and may have a linear relationship to the initial concentration.