Adhesive interactions mediated by integrins of the beta(1) subfamily(1) are thought to be critical in controlling differentiation and migration of blood cell precursors(2-7). Here we report that chimaeric mice generated with beta(1)-integrin-deficient embryonic stem (ES) cells(8,9) lack beta(1)(-/-) cells in blood and in haematopoietic organs such as spleen, thymus and bone marrow. Chimaeric embryos contain beta(1)-null haematopoietic cells in the yolk sac and in fetal blood but not in fetal liver. We show that such beta(1)(-/-) haematopoietic stem cells derived from yolk sac of 10.5-day-old chimaeric embryos readily generate erythroid and myeloid colonies and that beta(1)(-/-) ES cells can differentiate into mature B lymphocytes in vitro. Our results indicate that haematopoietic stem cells lacking beta(1) integrins can form and differentiate into different lineages but cannot colonize the fetal liver.