Seventeen IgA-deficient blood donors, without antibodies to IgA, underwent plasmapheresis four to eight consecutive times at intervals of 8 weeks or less to provide fresh-frozen plasma for patients with anti-IgA. Blood samples, drawn for analysis no more than 1 hour before plasmapheresis and again at the conclusion of each procedure, were analyzed for lymphocyte subpopulations and serum IgA levels. Five lymphocyte subpopulations, including natural killer cells, the suppressor-inducer CD4 subset, the suppressor-precursor CD8 subset, non-major histocompatibility complex (MHC)-restricted cytotoxic T cells, and CD5+ B cells, were all decreased significantly after plasmapheresis (p less than 0.05). In a subgroup of IgA-deficient donors with excessive IgA-suppressor T-cell activity, serum IgA increased to levels exceeding 0.05 g per L following the fourth consecutive plasmapheresis procedure. Serum IgA levels did not similarly increase in IgA-deficient donors without excessive IgA-suppressor T-cell activity or in controls without IgA deficiency. Our study shows the potential, in a subpopulation of IgA-deficient donors who undergo frequent plasmapheresis, for a transient increase in serum IgA to a level no longer considered IgA deficient.