Human peripheral blood lymphocytes were stimulated by concanavalin A, sodium periodate, and neuraminidase plus galactose oxidase. Response to mitogens was measured by the amount of tritiated thymidine incorporated as well as the percent of “giant sheep red blood cell rosettes” generated. The thymidine incorporation was diminished by the absence of monocytes or the presence of corticosteroids. The percent of giant rosettes generated was not influenced by either change. This finding suggested that considerable lymphocyte activation could still take place in the presence of corticosteroids. When subjects received 60 mg of prednisone, they developed lymphopenia 5 hr later. The circulating lymphocytes at that time responded less well to mitogen stimulation when measured by both thymidine incorporation and percent giant rosettes, suggesting a selective sequestration of mitogen-responsive lymphocytes outside the circulatory compartment.