The expression of the human serglycin gene was determined in nine human leukemic cell lines, representing a spectrum of erythrocytic, megakaryocytic, monocytic, granulocytic, and lymphocytic potentialities. By Northern blot analysis, a 1.4 kb transcript was characterized in some of these cell lines, using a cDNA probe coding for human serglycin. Five of these cell lines, HEL, U-937, HL-60, K-562, and KU-812 were treated with phorbol myristic acetate to induce differentiation. Under these conditions the expression of the serglycin gene was modulated compared to the non-induced cells. HL-60, K-562, and KU-812 were also induced with dimethyl sulfoxide and retinoic acid; variations in serglycin transcript level were also observed. The present investigation establishes, at the nucleic acid level, the ability of various cells mimicking different stages in the developmental pathways of the haemopoietic lineage to synthesize proteoglycans belonging to the serglycin family. The results reported here led us to conclude that serglycin expression is closely associated with the haemopoietic cell differentiation pathway. The putative functions of serglycin in the haemopoietic system are briefly discussed.