Recently, a new method and pharmaceutical formulation have been found that induce tolerance mucosally, such as by intranasal administration. The potential of mucosally administered antigens to inhibit immune responses in an antigen specific fashion has encouraged attempts to apply these routes to counteract immune dysfunctions such as allergies and in particular, autoimmune disease. Intranasal administration of E-selectin induces tolerance to E-selectin and leads to immune-deviation of a subset of lymphocytes such that they can suppress activation of vessel segments that are beginning to express E-selectin. Thus the ability of intranasal E-selectin treatment to decrease stroke lesions and delay the onset of stroke in stroke-prone spontaneously hypertensive rats suggests that the initial vessel activation and damage in stroke may be immunologically mediated. Production of immunosuppression via antigen-specific modulation of the immune response (mucosal tolerance) should have no systemic immunosuppressive effects.