Completed randomized placebo-controlled phase I/II studies of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) have demonstrated that this recombinant Mpl ligand has potent and lineage-dominant effects on megakaryopoiesis and platelet production. Platelets produced after PEG-rHuMGDF administration display normal ultrastructure and functional attributes. In these early studies, PEG-rHuMGDF accelerated the recovery of baseline platelet counts after cytotoxic chemotherapy in cancer patients by six to seven days, indicating the potential for clinical benefit in this setting. PEG-rHuMGDF has been well-tolerated in clinical trials, with similar adverse events in placebo and PEG-rHuMGDF populations, and an observed adverse event profile consistent with the effects of underlying malignancy and chemotherapy. The lack of inflammatory cytokine effects in the clinic is consistent with results of animal studies, the narrow tissue distribution of Mpl and the lineage-dominant effect of PEG-rHuMGDF on megakaryopoiesis. Additional phase I/II studies have commenced in the fields of cancer chemotherapy and augmentation of platelet donation, and a phase III study is underway in patients undergoing bone marrow transplantation.