Myelin P2 protein has been proposed as the primary antigen in whole myelin-induced experimental allergic neuritis (EAN). We investigated the neuritogenic properties of P2 by sensitizing Lewis rats with complete Freund's adjuvant (CFA) containing P2, P2 plus phosphatidyl serine, or whole myelin containing an equivalent amount of P2. Animals were examined using a battery of clinical, electrophysiological, immunological, and morphological methods. Myelin-immunized rats developed the characteristic features of EAN. P2-sensitized rats developed a similar but much less intense disorder. When rats were sensitized with P2 in the presence of phosphatidyl serine, however, they developed radiculoneuropathy that was indistinguishable from myelin-induced EAN. Inoculation with phosphatidyl serine plus complete Freund's adjuvant or complete Freund's adjuvant alone had no detectable effect on peripheral nerves. These studies demonstrate that sensitization of rats with a single myelin antigen, P2 protein, is sufficient to induce the clinical, electrophysiological, and neuropathological features of EAN.