Enumeration of total lymphocytes and T, B, and null lymphocyte subpopulations in peripheral blood of normal volunteers was performed before and at intervals after inoculation with type A influenza virus. Volunteers who subsequently developed infection and illness had larger T-cell counts before inoculation and exhibited an increased number of B lymphocytes during the incubation period and a decrease in all subpopulations during illness, although the greatest decrease occurred in T cells. A decrease in B-cell counts occurred on day 3 in volunteers who exhibited infection, but no illness and no changes occurred in uninfected, well volunteers. Values had returned to baseline by day 21 after inoculation. Thus, the lymphopenia that accompanies influenza involves all subpopulations, but is primarily a decrease in T cells; in addition, differences in T-cell and B-cell populations before and during the incubation period may identify persons who will subsequently develop febrile influenza.