The nature and kinetics of the serum antibody response to pneumococcal type 3 and meningococcal group C polysaccharides and their protein conjugates were studied in mice. Bovine serum albumin and diphtheria and tetanus toxoids were used as carrier proteins. The purified polysaccharides induced only immunoglobulin M (IgM) antibodies in thymus-bearing as well as congenic athymic (nude) mice. The polysaccharides covalently conjugated to proteins produced IgM and IgG antibodies in normal mice, but only IgM antibodies in nude mice. A second dose of the polysaccharide-protein conjugates resulted in a booster effect in the IgG response to the polysaccharides. Moreover, memory B-cells, generated after a primary injection with the polysaccharide-protein conjugates, could be triggered to the production of IgG antibodies after a second injection with the pure polysaccharides alone. These data indicate that the antibody response to the pure polysaccharides is thymus independent and that this response can be changed into a thymus-dependent response by covalent conjugation of the polysaccharide to a thymus-dependent protein.