A model for chronic Cryptococcus neoformans meningitis in corticosteroid-treated rabbits was used to determine the influence of pre-formed agglutinating antibody to cryptococcal polysaccharide on the progress of this infection. Immunized rabbits developed serum agglutinating antibody with a geometric mean titre of 1:32, but none was detected in cerebrospinal fluid. Prior immunization did not enhance immunity to infection, had no effect on the number of viable cryptococci in cerebrospinal fluid, and did not prevent dissemination outside the central nervous system. Future investigations in this field should focus on cellular rather than humoral defence mechanisms.