The recombinant thrombopoietins have been shown to be effective stimulators of platelet production in cancer patients. It was therefore of interest to determine if one of these, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), could be used to increase platelet counts and consequently platelet yields from apheresis in healthy platelet donors. In a blinded, 2-cycle, crossover study, 59 platelet donors were randomized to receive a single subcutaneous injection of PEG-rHuMGDF (1 μg/kg or 3 μg/kg) or placebo and 15 days later undergo platelet apheresis. Donors treated with placebo had a median peak platelet count after PEG-rHuMGDF injection of 248 × 109/L compared with 366 × 109/L in donors treated with 1 μg/kg PEG-rHuMGDF and 602 × 109/L in donors treated with 3 μg/kg PEG-rHuMGDF. The median maximum percentage that platelet counts increased from baseline was 10% in donors who received placebo compared with 70% in donors who received 1 μg/kg and 167% in donors who received 3 μg/kg PEG-rHuMGDF. There was a direct relationship between the platelet yield and the preapheresis platelet count: Placebo-treated donors provided 3.8 × 1011 (range 1.3 × 1011-7.9 × 1011) platelets compared with 5.6 × 1011 (range 2.6 × 1011-12.5 × 1011) or 11.0 × 1011 (range 7.1 × 1011-18.3 × 1011) in donors treated with 1 μg/kg or 3 μg/kg PEG-rHuMGDF, respectively. Substandard collections (<3 × 1011 platelets) were obtained from 26%, 4%, and 0% of the placebo, 1 μg/kg, and 3 μg/kg donors, respectively. No serious adverse events were reported; nor were there events that met the criteria for dose-limiting toxicity. Thrombopoietin therapy can increase platelet counts in healthy donors to provide a median 3-fold more apheresis platelets compared with untreated donors.