Stathmin is a cytosolic phosphoprotein that has an important but, as yet, undefined role in cell proliferation and differentiation. Induction of growth arrest and differentiation of HL60 cells to monocytes by phorbol 12-myristate 13-acetate is associated with rapid phosphorylation of the protein. Stathmin phosphorylation was not seen when HL60 cells were induced to differentiate to monocytes, by 1 alpha, 25-dihydroxyvitamin D3, and to neutrophils, by all-trans retinoic acid and granulocyte colony stimulating factor. In all the above instances, stathmin expression was down-regulated. Thus, increased stathmin phosphorylation is not required for cell growth arrest or differentiation or down-regulation of stathmin expression.