We have previously reported changes in the immunoresponsiveness of "T" lymphocytes following space flight. Additional data collected before and after 11 Shuttle space flights show that absolute lymphocyte numbers, lymphocyte blastogenic capability, and eosinophil percent in the peripheral blood of crewmembers are generally depressed postflight. These responses resemble those associated with physical and emotional stress and may not be related to flight per se. Additional data from Space Shuttle flights 41B and 41D, involving 11 crewmembers, indicate a postflight decrease in cells reacting with "B" lymphocyte and monocyte monoclonal antibody tags. Further, the loss of "T" lymphocyte blast capability interacts with the decreased monocyte count (correlation coefficient = 0.697). This finding implies that the previously reported loss of blastogenic capability may be a function of decreased monocyte control, as noted in several non-spaceflight related studies.