The neuropathology core provides services essential to all four projects. As detailed in the projects, histopathological changes are the critical end point for many of the proposed experiments. Tissue specimens are acquired by the core as part of the experimental procedures. Animals are rarely dedicated solely to acquisition of samples for this core. Exceptions are those procedures (plastic embedding and EM) which require perfusion with fixative. Times of tissue acquisition are dictated by the individual experiments and are coordinated by the core director. The core research associate is responsible for processing, sectioning and staining of all tissues. Routine examinations, carried out on the majority of animals include H&E, luxol fast blue for myelin and immunoperoxidase determinations for the distribution of viral Ag. Special stains for specific subtypes of cells, expression of cytokines, in situ hybridization's etc., are dictated by the individual experiments and are also quality controlled and scheduled in conjunction with the core director. Epon embedded materials and frozen sections are also processed by the core. We are fortunate to have retained the services of Wen for the past 13 years. He has experience in all of the proposed techniques and has been an invaluable asset to our ongoing research efforts. In the past we have published precise protocols for all of the proposed techniques and therefore no difficulties are anticipated. Detailed methods will not be reiterated here. Depending upon the nature of the experiments, slides are either screened by the core director or Dr. Hinton or both, in a blinded fashion. Blinded reading of critical experiments eliminates investigator bias.