Cultured neurons isolated from the embryonic day 18 (E18) rat cortex were plated onto cryostat sections of adult CNS and peripheral nerve. The ability of these sections to support neuronal attachment and neurite extension was compared to that of neurons on the adjacent poly-L-lysino (PLL)-coated glass coverslips. A quantitative analysis of the data demonstrated that sections of cerebral cortex provide a good substrate for neuronal attachment and growth of neurites, similar to that of the PLL-coated glass coverslips. Sections of sciatic nerve demonstrated a decreased ability to sup port neuronal attachment and the growth of processes as compared to sections of cortex. Sections of opticnerve supported limited neuronal attachment, and the few neurons that were present on top of the sections were devoid of processes. Control experiments showed that the ability of the cortical sections to support the attachment and growth of cultured neurons was due to the molecular composition of the sections and not to influences of the tissue culture environment. The interactions of neurons with the sections of CNS cortex were partially dependent on a member of the β1integrin family of extracellular matrix receptors present on cultured neurons. This in vitro system allowed for the definition of some of the molecular and the cellular interactions that may occur between growing axons and the environment of the adult cortex.