This study has determined the effects of phorbol-12-myristate-13-acetate (PMA) and dimethylsulfoxide (DMSO) on mRNA levels for the serglycin proteoglycan core protein in human erythroleukemia (HEL) cells. We have compared these changes to those for mRNA for other proteins which are known to be synthesized by HEL cells and megakaryocytes and are known to be localized to alpha granules within platelets. PMA caused a large increase in mRNA for serglycin within two hours of treatment of the cells, and the increase persisted for at least 72 hours. DMSO did not cause a significant change in mRNA levels. mRNA for platelet factor 4, transforming growth factor-beta, and P-Selectin (PADGEM, GMP-140) were also increased by PMA treatment. The mRNA for platelet factor 4 was substantially reduced in the presence of DMSO. The increase of mRNA for serglycin induced by PMA was consistent with our previous observation that synthesis of proteoglycans from [35S]sulfate was greatly stimulated by PMA in HEL cells. The data suggest that up-regulation of synthesis of proteoglycans is induced by PMA in cells which have the capacity to differentiate along the megakaryocytic lineage, as opposed to cell lines such as HL-60 in which proteoglycan synthesis is reduced in the presence of this differentiation-inducing agent.