The neurologic manifestations of Lyme disease include meningitis, radiculoneuritis, and cranial neuritis. In two patients, we investigated the proliferative response of CSF and peripheral blood lymphocytes to protein antigens derived from the Lyme disease spirochete. The response of CSF lymphocytes was 5 to 10 times greater than that of peripheral blood lymphocytes. In contrast, in the one patient studied, lectin-induced proliferation was less in CSF than in peripheral blood. These findings show that the CSF of patients with Lyme meningitis is an enriched source of antigen-specific proliferative lymphocytes.