Staphylococcal Enterotoxin A (SEA) at picogram amounts induces high levels of interleukin 2 (IL-2) and interferon in human mononuclear cells. SEA is a stronger inducer of IL-2 than phytohemagglutinin, leukoagglutinin, and concanavalin A. The IL-2 induction is very rapid with maximal levels being reached after 18 to 24 hr. The IL-2 concentration decreases rapidly and almost no IL-2 activity can be detected in supernatants of cells cultured for 3 days or more. Maximal DNA synthesis is recorded 3 days after maximal IL-2 levels have been reached in the culture medium. The DNA synthesis shows a 24 hr delay as compared to the expression of the IL-2 receptor during the initiation phase. An increase in the level of IL-2 receptor expression is apparent as early as 12 hr after stimulation with SEA and maximal expression is reached 48 to 72 hr after stimulation. The percentage of cells expressing the IL-2 receptor is maximal at 96 hr after onset of culture but the surface concentration of the receptor is lower than at 72 hr. The decline in expression of the IL-2 receptor is accompanied by a decline in mean cell size and in DNA-synthesis. The concentration of the T-cell marker T11 increases in parallel with the growing expression of the IL-2 receptor. It remains increased over a longer period than the IL-2 receptor and is still significantly augmented after 10 days' exposure to SEA.