Haematopoiesis involves the differentiation of a self-renewing stem cell into all of the lineages found in circulating blood. Myb-Ets transformed chicken blastoderm cells (MEPs) have many of the characteristics of multipotent haematopoietic cells and represent a useful model system for the study of haematopoiesis. The proline-rich homeodomain protein (PRH) has previously been shown to be expressed in the haematopoietic compartment. In this report we show that PRH mRNA and protein levels are down regulated as MEPs differentiate along the myelomonocytic and erythrocytic lineages. In contrast, PRH mRNA and protein levels remain high as MEPs differentiate toward the thrombocytic lineage. Over-expression of full length PRH in MEPs inhibits their transformation and/or proliferation. However, the over-expression of N-terminally truncated PRH proteins results in normally proliferating cells that are predominantly differentiated along the myelomonocytic and eosinophilic lineages. These results suggest that PRH plays a role in the proliferation and differentiation of haematopoietic cells.