In 190 pregnancies undergoing cordocentesis for prenatal diagnosis (n = 174) or elective caesarean section (n = 16), fetal peripheral blood B lymphocyte subpopulations were measured using a fluorescence-activated cell sorter (FACScan). The total number of B lymphocytes and polyreactive CD 5+ B cells increased exponentially with gestation from respective means of 0.33 × 109/1 and 0.25 × 109/1 at 17 weeks to a plateau of 0.66 × 109/1 and 0.54 × 109 at 36 weeks, remaining at that level thereafter. The number of mature CD 10- and active CD23+ B lymphocytes increased linearly from a mean of 0.07 × 109/1 and 0.11 × 109/1 at 17 weeks to 0.24 × 109/1 and 0.37 × 109/l, respectively, at 40 weeks. As expected, all B lymphocytes expressed the HLA-DR antigen from as early as 16 weeks gestation. These alterations in specific B lymphocyte subpopulations reflect the pattern of maturation and development of the fetal humoral immune