Hemolytic disease of newborn due to anti-K, an antibody of the Kell blood group system, is associated with low circulating reticulocytes. Also, the antibody titer and bilirubin levels are not reliable predictors of anemia. These observations suggest that anti-K antibodies (Abs) may affect erythropoiesis. The inhibitory effect of the antibodies was studied in vitro using mononuclear cells isolated from cord blood. The generation of BFU/CFU-E colonies was evaluated in the presence of maternal anti-K, commercially available monoclonal IgM anti-K, polyclonal IgG anti-K and anti-k, and with a murine anti-Kell glycoprotein antibody. Also, the effect of anti-Kell blood group Abs was evaluated in the presence of excess monomeric IgG, and on purified CD34+ cells. All Abs significantly inhibited erythroid colony formation (p < 0.05). The inhibitory effect was maintained in presence of monomeric IgG and with purified CD34+ cells. Results reveal that anti-Kell Abs directly inhibit erythropoiesis.