The human gene encoding the differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) receptor was cloned and its structure was analyzed. The gene spans more than 70 kilobases and contains 20 exons. The D-factor/LIF receptor can be subdivided into several regions: cytokine receptor homologous domain 1, an Ig-like domain, cytokine receptor homologous domain 2, three fibronectin type III domains, a transmembrane domain and a cytoplasmic region. Each domain of the receptor is encoded by a set of exons. There is a TATA sequence upstream of the transcription initiation site. One unit of the Alu sequence is present in the 5' flanking region. An NF-IL6 site is located 31 bases downstream of the transcription initiation site.