Twenty-two normal volunteers had approximately eight, 2-hr-long leukapheresis procedures over a 2-year period and their natural killer (NK) cell function was prospectively measured. The NK activity of the preprocedure peripheral blood (pre-PB) was found to correlate well with the NK activity of the inital leukocytes removed by leukapheresis (I-Leuk). When the I-Leuk specimens were compared with the leukapheresis specimens removed at the termination of leukapheresis (T-Leuk), T-Leuk showed a consistent 10% increase in NK activity. When the pre-PB and the I-Leuk values were analyzed for each donor over the 2 years of the study, 18 donors revealed no significant change from their baseline NK activity, two donors showed a minimal increase in NK cell activity, and two donors displayed a minimal decrease in NK cell activity. We conclude that although leukapheresis appears acutely to boost NK cell activity, this increase is transient and small in magnitude. Most importantly, repeated leukapheresis does not appear adversely to effect this important effector function in normal donors.