The National Marrow Donor Program (NMDP) has been facilitating hematopoietic cell transplants since 1987. Volunteer donors listed on the NMDP Registry may be asked to donate either bone marrow (BM) or peripheral blood stem cells (PBSC); however, since 2003, the majority of donors (72% in 2007) have been asked to donate PBSC. From the donor's perspective these stem cell sources carry different recovery and safety profiles. The majority of BM and PBSC donors experienced symptoms during the course of their donation experience. Pain is the number 1 symptom for both groups of donors. BM donors most often reported pain at the collection site (82% back or hip pain) and anesthesia-related pain sites (33% throat pain; 17% post-anesthesia headache), whereas PBSC donors most often reported bone pain (97%) at various sites during filgrastim administration. Fatigue was the second most reported symptom by both BM and PBSC donors (59% and 70%, respectively). PBSC donors reported a median time to recovery of 1 week compared to a median time to recovery of 3 weeks for BM donors. Both BM and PBSC donors experienced transient changes in their WBC, platelet, and hemoglobin counts during the donation process, with most counts returning to baseline values by 1 month post-donation and beyond. Serious adverse events are uncommon, but these events occurred more often in BM donors than PBSC donors (1.34% in BM donors, 0.6% in PBSC donors) and a few BM donors may have long-term complications. NMDP donors are currently participating in a randomized clinical trial that will formally compare the clinical and quality-of-life outcomes of BM and PBSC donors and their graft recipients.