The involvement of the central nervous system (CNS) in lepromatous leprosy (LL) patients was investigated; 33 patients were examined clinically in detail and upper motor neuron involvement was observed in eight and lower motor neuron in three of these patients. Anti-Mycobacterium leprae antibodies could be detected in the CSF by PGL-1 enzyme-linked immunosorbent assay (ELISA) and monoclonal antibody (MAb) based competitive assays against defined epitopes on the 35-kDa protein and 30-40-kDa polysaccharide (lipoarabinomannan) antigens with MAbs MLO4 and ML34, respectively. Antibodies against PGL-1 and 35-kDa protein were observed in more subjects than antibodies against the 30-40-kDa antigen. Some correlation was observed between the upper motor neuron signs and antibody positivity for 35-kDa and PGL-1 antigens in the CSF of these patients.