Future spaceflight will require travelers to spend ever‐increasing periods of time in microgravity. Optimal functioning of the immune system is of paramount importance for the health and performance of these travelers. A meta‐analysis statistical procedure was used to analyze immune system data from crew members in United States and Soviet space missions from 8.5 to 140 days’duration between 1968 and 1985. Ten immunological parameters (immunoglobulins A, G, M, D, white blood cell [WBC] count, number of lymphocytes, percent total lymphocytes, percent B lymphocytes, percent T lymphocytes, and lymphocyte reactivity to mitogen) were investigated using multifactorial, repeated measure analysis of variance. With the preflight level set at 100, WBC count increased to 154±14% (mean±SE; p≤0.05) immediately after flight; there was a decrease in lymphocyte count (83±4%; p≤0.05) and percent of total lymphocytes (69±1%; p≤0.05) immediately after flight, with reduction in RNA synthesis to phytohemagglutinin (PHA) to 51±21% (p≤0.05) and DNA synthesis to PHA to 61±8% (p≤0.05) at the first postflight measurement. Thus, some cellular immunological functions are decreased significantly following spaceflight. More data are needed on astronauts’age, aerobic power output, and parameters of their exercise training program to determine if these immune system responses are due solely to microgravity exposure or perhaps to some other aspect of spaceflight.