Several mouse and human genes encoding the DNA-binding homeobox domain are implicated here in haematopoiesis, a differentiation process maintained throughout life. Four homeobox cDNA clones were isolated from bone marrow and spleen of adult mice and two from the human leukaemia cell line K562. They derive from the Hox 1.1, Hox 2.3, Hox 6.1 genes and two previously undescribed genes, one of a type (paired) not found before in vertebrates. A survey of 36 cell lines of the lymphoid, myeloid and erythroid lineages revealed that certain homeobox transcripts were almost ubiquitous, while others were restricted to certain lineages or even particular cell lines. The expression pattern altered in a myeloid and an erythroid line induced to terminal differentiation, and in novel lines that had switched from a lymphoid to a myeloid phenotype. Altogether, the haemopoietic compartment may contain up to 20 homeobox transcripts. In one myeloid leukaemia, DNA rearrangement has perturbed expression. These findings suggest that homeobox genes may influence developmental decisions within the haemopoietic system.