In order to gain insight into the relatively late appearance in ontogeny of responsiveness to T-cell independent (TI) antigens, the in vitro human B-cell response to type 4 pneumococcal polysaccharides (PS4, a human TI-2 antigen) was studied. B cells obtained from adults differentiate into anti-PS4 antibody forming cells upon culturing with PS4, but neonatal B cells obtained from cord blood fail to respond. The culture system used does, however, allow the differentiation of B cells reactive with TD antigens, for example ovalbumin. In order to evaluate the concept that in man the anti-PS4 response is derived from a particular B-cell subset we separated adult B cells on the basis of expression of the determinant recognized by the monoclonal antibody FMC7. The anti-PS4 response is found mainly, but not exclusively, in the FMC7+ subset. The selective unresponsiveness of neonatal B cells to TI-2 antigens is not, however, due to the absence of FMC7+ B cells because, unlike adult blood B cells of which about 50% are FMC7+, 100% of neonatal B cells are FMC7+.