The treatment with ACTH induced high, but physiological, concentrations of cortisol in plasma. Simultaneously, the number of lymphocytes per milliliter blood decreased while the neutrophil number increased. The elevated concentrations of cortisol also coincided with reduced proliferation and interleukin-2 production by blood lymphocytes stimulated with the mitogens concanavalin A and phytohemagglutinin in vitro, while the responses to pokeweed mitogen were less affected. The suppression of mitogen responses was more pronounced in cultures of whole blood than in cultures of purified peripheral blood mononuclear cells (PBMC).