The recombinant hemopoietic factors of megakaryocyte potentiator (MEG-POT) were studied to compare their activity in stimulating proplatelet process formation (PPF) with thrombopoietin (TPO, c-MpI ligand). For the assay, a highly enriched (> 95%) population of more than 90% viable megakaryocytes was isolated from rat bone marrow using the immunomagnetic beads method and cultured with fetal calf serum (FCS) or in a serum-free condition. Megakaryocytes developing slender beaded cytoplasmic processes (proplatelet processes) were observed on both inverted phase contract microscopy and scanning electron microscopy. A large number of proplatelet process clusters were dose-dependently formed with the addition of varying doses of recombinant erythropoietin (rEpo) and interleukin-6 (rIL-6) as well as TPO. Epo and IL-6 were demonstrated to act synergistically solely at low doses in the development of PPF (P < 0.05). Other recombinant factors such as IL-11, leukemia inhibitory factor (LIF) and erythroid differentiation factor (EDF) appeared weak or ineffective. From these in vitro observations, it was suggested that a synergism of Epo and IL-6 might play a significant role in the terminal stage of megakaryocyte maturation leading to platelet release.