Several in vitro measurements of immune function were examined retrospectively in a population of active long-term cytapheresis donors (group I; n = 50) and the results were compared to age- and sex-matched controls (group II; n = 50) who had donated only whole blood. In group I, significantly different mean absolute lymphocyte counts (P = .0025), total T-cells (P = .0026) and T-helper cells (P less than .0001), and helper-to-suppressor ratios (P = .0279) were present. No differences were noted between the two groups for peripheral blood mean B-cell count, T-suppressor numbers, lymphocyte responsiveness to mitogens or alloantigen, and serum immunoglobulin level. The reduced mean absolute lymphocyte count in group I was due to the reduction in T-helper cell numbers and accounted for the imbalance in the helper-to-suppressor ratio. These disturbances are currently unexplained and, while no clinical consequences have so far become evident, there is a need to continuously monitor the immunologic status of cytapheresis donors. It is also important to determine whether reversal of the defects occurs and, if so, over what time interval.