The administration of granulocyte colony-stimulating factor (G-CSF) to increase the white blood cell count in granulocyte donors prior to donation is becoming an increasingly common practice. G-CSF is given subcutaneously to the donor on the day prior to donation, generally 12 to 24 hours before the start of apheresis. G-CSF has also been given for 5 days to hematopoietic stem cells donors prior collecting peripheral blood stem cell(PBSC)concentrates by apheresis. PBSC concentrate donors given G-CSF experience splenic enlargement and rarely, spontaneous rupture of the spleen. This study evaluated the incidence and time course of splenic enlargement in PBSC concentrate donors and accessed factors effecting size changes. Twenty healthy adult PBSC concentrate donors were given G-CSF (10 mg/kg/day) for 5 days. Ultrasound was used to assess craniocaudal spleen length prior to giving G-CSF, the day of apheresis, and 3 or 4 days after apheresis. The effects of donor age, gender, race and changes in blood chemistries, blood counts, and CD34+ cell counts on spleen length change was assessed. Spleen length increased in 19 of 20 donors. Mean length changed from 10.7 cm pre-G-CSF to 12.3 cm on the apheresis day (p < 0.002). Three or four days after apheresis the spleen length fell to 11.3 cm (p<0.001), but remained greater than baseline levels (p=0.04). There was no difference in spleen length change among males and females or among Caucasians and non-Caucasians. There was no relationship between subject age and change in length or percent change in length. There was no relationship between baseline blood counts and chemistries and change in apheresis day size but apheresis day alkaline phosphatase and total bilirubin levels were related to change in length. These studies found that spleen size increases in almost all PBSC donors. Enlargement is transient but marked in some donors and may place donors at risk for splenic rupture. Greater collection day alkaline phosphatase, bilrubin and neutrophil levels were associated with greater increases in spleen size. Future studies will focus on identifying factors that predict which donor will have a very large increase in spleen size.