Lymphocyte losses occur during repeat plateletpheresis and/or leukapheresis procedures and are potentially harmful to normal host immune function. This concern prompted us to study the effect of repeat lymphocytapheresis (lymphapheresis) on the immune system of healthy blood donors. Following a total of six lymphapheresis procedures over a 12-day period with removal of a mean of 41.6 x 10^9 lymphocytes, there were no significant changes in donor (n = 5) absolute lymphocyte counts, quantitative immunoglobulin levels or immune response capability as assessed by the following in vitro assays: percent of E, EA, and EAC rosette-forming cells, the percent of surface membrane immunoglobulin bearing cells, and the blastogénie responses to stimulation with phytohemagglutinin, pokeweed mitogen and concanavalin A. The procedures were well-tolerated without complications. During a follow-up period of 18 months, significant increases in total white cell counts (but not absolute lymphocyte counts), and in quantitative immunoglobulin levels (IgG, IgM, and IgA) were observed. The median increases in immunoglobulin levels ranged from 27.5% for IgG to 44% for IgA. We conclude that lymphapheresis as described is relatively safe and our results are reassuring in relation to lymphocyte losses that may occur during repeat cytapheresis procedures of normal blood donors.