The antibody response to a variety of antigens, including pneumococcal polysaccharides, is diminished in splenectomized (splx) mice. We investigated the capacity for the biological response modifier Corynebacterium parvum to augment antibody production in splx and sham-splx mice inoculated with pneumococcal polysaccharides and tetanus toxoid. As expected, antibody response to tetanus toxoid was similar in both splx mice and sham-splx mice. C. parvum augmented anti-tetanus toxoid antibody in both sham-splx (P less than 0.05) and splx mice (P less than 0.05). Antibody against pneumococcal type 3 polysaccharides was decreased in splx mice compared with sham-splx mice (P less than 0.05). Both groups treated coincidently with C. parvum and pneumococcal type 3 polysaccharides demonstrated a biphasic antibody response which was greater than that observed in saline-treated controls (sham-splx, P less than 0.001; splx, P less than 0.05). Whereas the secondary peak response to pneumococcal type 3 polysaccharides after treatments with C. parvum appears to be due to persistent elevations of immunoglobulin G and immunoglobulin M in sham-splx mice, it is primarily due to antibody of the immunoglobulin G class alone in the splx mice.