Adhesive interactions mediated by integrins of the beta1 subfamily are thought to be critical in controlling differentiation and migration of blood cell precursors. Here we report that chimaeric mice generated with beta1-integrin-deficient embryonic stem (ES) cells lack beta1(-/-) cells in blood and in haematopoietic organs such as spleen, thymus and bone marrow. Chimaeric embryos contain beta1-null haematopoietic cells in the yolk sac and in fetal blood but not in fetal liver. We show that such beta1(-/-) haematopoietic stem cells derived from yolk sac of 10.5-day-old chimaeric embryos readily generate erythroid and myeloid colonies and that beta1(-/-) ES cells can differentiate into mature B lymphocytes in vitro. Our results indicate that haematopoietic stem cells lacking beta1 integrins can form and differentiate into different lineages but cannot colonize the fetal liver.