Peripheral blood stem cell (PBSC) collection was evaluated in two groups of normal donors who underwent large-volume leukapheresis on a blood cell separator. In Group A (n = 10), a 3-hour leukapheresis was performed. An average of 11.8 L of blood was processed with a mean flow rate of 66 mL per minute and a collection rate of 3 mL per minute. The PBSC product contained a mean 1.4 x 10(10) mononuclear cells (MNCs) (lymphocytes and monocytes), 1.27 x 10(6) colony-forming units-granulocyte-macrophage (CFUs-GM), and an average hematocrit of 4 percent (0.04). Postapheresis blood counts showed significant reductions in MNCs (19%) and platelets (45%) (p less than 0.005). Twenty-four hours later, the MNCs had returned to preapheresis levels. The platelet count returned to baseline only after 7 days. Circulating CFUs-GM remained stable for 3 days after apheresis but were increased twofold by Day 7 after apheresis (p = 0.025). Varying the product hematocrit from 1 percent (0.01) to 13.3 percent (0.13) did not change the number of CFUs-GM collected per MNC. In Group B (n = 4), an average of 18.5 L of blood was processed with a mean flow rate of 94 mL per minute and a collection rate of 3 mL per minute. The PBSC product was collected as four sequential samples and assayed for MNCs and CFUs-GM. Total MNCs averaged 1.7 x 10(10) (an increase of 21% relative to Group A) and CFUs-GM averaged 3.08 x 10(6) (an increase of 143%). Mean MNCs did not vary significantly among the four samples. However, CFUs-GM collected per minute (relative to the first sample) did show 1.26-fold (p = 0.001), 1.86-fold (p = 0.011), and 2.52-fold (p = 0.04) increases in the second, third, and fourth samples. These data suggest that MNCs and committed progenitor cells are recruited during large-volume leukapheresis. Moreover, there is a twofold increase in circulating CFUs-GM 1 week after apheresis.