It is believed that the expression of the conditioned natural killer cell activity is regulated through the hypothalamus-pituitary axis. Since the conditioned expression of both the plasma level of adrenocorticotropic hormone and natural killer (NK) cell activity show a sequential rise after exposure to the conditioned stimulus, it was of interest to determine if treatment with dexamethasone could inhibit this response. These studies suggest that treatment with dexamethasone was able to block the expression of the conditioned NK cell activity but was unable to interfere with the pairing of the conditioned stimulus with the unconditioned stimulus. We conclude that the hypothalamic pituitary axis is an integral part of the pathway for stimulation of NK cell activity in the spleen. © 1994 S. Karger AG, Basel.