BM processing, volume reduction, and granulocyte and erythrocyte depletion are important considerations for minimizing the side effects of graft administration and bypassing ABO incompatibility in allogeneic BMT. We used the COBE Spectra cell separator for BM processing in 33 patients suffering from hematologic malignancy and solid tumor (median age 39 years). We processed 42 BM harvests with the aim of maximizing recovery of mononuclear cells (MNC). BM was collected from the posterior iliac crest under general anesthesia. The mean volume of collected BM before filtration was 1,303 ml, and the mean number of collected total nucleated cells (TNC) was 2.61 x 10(8)/kg. The BM processing resulted in a mean recovery of 35.8% (10.1%-78.3%) TNC, 22.3% (1.1%-75.7%) of granulocytes, 78.8% (34.3%-135.2%) of MNC, 77.2% (8.3%-260.0%) of CD34+ cells, and 153.3% (32.9%-464.0%) of colony-forming units (CFU-GM) in the final product. A mean of 98.2% (94.5%-99.5%) of RBC was removed, with a mean of 13.3 ml (5.1-26.2 ml) of RBC in the final product. BM processing using the COBE Spectra cell separator proved to be fast, safe, and effective. However, the reasons for the very wide range of recovery of harvested CD34+ cells and CFU-GM need to be further investigated.