A hyperacute form of experimental autoimmune encephalomyelitis (HEAE) was induced in Lewis rats using small doses (3.2 mug) of guinea pig myelin basic protein as immunogen and B. pertussis vaccine as adjuvant. Myelin basic proteins from species other than guinea pig (rat, man, monkey, pig, ox, rabbit and sheep) induced only ordinary EAE with this adjuvant. HEAE was more readily distinguished from ordinary EAE by clinical criteria (early onset, with a rapid and severe course, and high incidence of cerebral signs and mortality) than by histologic signs which, although characteristic of HEAE. were not pathognomonic for HEAE, HEAE was transferred to x-irradiated syngeneic recipient rats with lymph node cells from appropriately immunized donors. The Brown Norway (BN) strain of rat was found susceptible to induction of ordinary EAE, but not HEAE, using large doses of either rat or guinea pig myelin basic proteins. The unique immunogenicity of the guinea pig basic protein must be due to a different antigenic determinant from the determinant(s) which is shared by rat and guinea pig myelin basic proteins and which without B. pertussis induces ordinary EAE. The adjuvant action of B. pertussis in inducing HEAE in the Lewis rat is most likely mediated through an immunocompetent T lymphocyte.