As a prerequisite of inflammatory lesion formation in (auto‐)immune disease of the central nervous system, lymphocytes have to interact with brain endo‐thelia. In recent years much progress has been made towards a better understanding of mechanisms and factors involved in organ specific homing of lymphocytes. Many lines of evidence indicate that T lymphocytes recognizing antigens which are exclusively beyond the blood‐brain barrier cross this barrier only when they are in an activated state, irrespective of their antigen specificity. Antigen presentation by blood‐brain barrier endothelia, however, may play a role in later stages of florid infla